Solidarity and reciprocity during the COVID-19 pandemic: a longitudinal qualitative interview study from Germany.

BACKGROUND: While solidarity practices were important in mitigating the Coronavirus Disease 2019 (COVID-19) pandemic, their limits became evident as the pandemic progressed. Taking a longitudinal approach, this study analyses German residents' changing perceptions of solidarity practices during the COVID-19 pandemic and examines potential reasons for these changes. METHODS: Adults living in Germany were interviewed in April 2020 (n = 46), October 2020 (n = 43) and October 2021 (n = 40) as part of the SolPan Research Commons, a large-scale, international, qualitative, longitudinal study uniquely situated in a major global public health crisis. Interviews were analysed using qualitative content analysis. RESULTS: While solidarity practices were prominently discussed and positively evaluated in April 2020, this initial enthusiasm waned in October 2020 and October 2021. Yet, participants still perceived solidarity as important for managing the pandemic and called for institutionalized forms of solidarity in October 2020 and October 2021. Reasons for these changing perceptions of solidarity included (i) increasing personal and societal costs to act in solidarity, (ii) COVID-19 policies hindering solidarity practices, and (iii) a perceived lack of reciprocity as participants felt that solidarity practices from the state were not matching their individual efforts. CONCLUSIONS: Maintaining solidarity contributes to maximizing public health during a pandemic. Institutionalized forms of solidarity to support those most in need contribute to perceived reciprocity among individuals, which might increase their motivation to act in solidarity. Thus, rather than calling for individual solidarity during times of crisis, authorities should consider implementing sustaining solidarity-based social support systems that go beyond immediate crisis management.

Relationship between mental health diagnoses and COVID-19 test positivity, hospitalization, and mortality in Southeast Wisconsin.

BACKGROUND: There is a paucity of literature on the relationship between pre-existing mental health conditions and coronavirus disease-2019 (COVID-19) outcomes. The aim was to examine the association between pre-existing mental health diagnosis and COVID-19 outcomes (positive screen, hospitalization, mortality). METHODS: Electronic medical record data for 30 976 adults tested for COVID-19 between March 2020 and 10th July 2020 was analyzed. COVID-19 outcomes included positive screen, hospitalization among screened positive, and mortality among screened positive and hospitalized. Primary independent variable, mental health disorders, was based on ICD-10 codes categorized as bipolar, internalizing, externalizing, and psychoses. Descriptive statistics were calculated, unadjusted and adjusted logistic regression and Cox proportional hazard models were used to investigate the relationship between each mental health disorder and COVID-19 outcomes. RESULTS: Adults with externalizing (odds ratio (OR) 0.67, 95%CI 0.57-0.79) and internalizing disorders (OR 0.78, 95% CI 0.70-0.88) had lower odds of having a positive COVID-19 test in fully adjusted models. Adults with bipolar disorder had significantly higher odds of hospitalization in fully adjusted models (OR 4.27, 95% CI 2.06-8.86), and odds of hospitalization were significantly higher among those with externalizing disorders after adjusting for demographics (OR 1.71, 95% CI 1.23-2.38). Mortality was significantly higher in the fully adjusted model for patients with bipolar disorder (hazard ratio 2.67, 95% CI 1.07-6.67). CONCLUSIONS: Adults with mental health disorders, while less likely to test positive for COVID-19, were more likely to be hospitalized and to die in the hospital. Study results suggest the importance of developing interventions that incorporate elements designed to address smoking cessation, nutrition and physical activity counseling and other needs specific to this population to improve COVID-19 outcomes.

Partial sequence conservation of SARS-CoV-2 NSP-2, NSP-12, and Spike in stool samples from Abadan, Iran.

Since the onset of the coronavirus disease 2019 (COVID-19) pandemic, the clinical manifestations of the virus have undergone many changes. Recently, there have been many reports on gastrointestinal symptoms in COVID-19 patients. This study is aimed to perform a detailed phylogenetic study and assessment of different SNVs in the RNA genome of viruses isolated from fecal samples of patients with COVID-19 who have gastrointestinal symptoms, which can help better understand viral pathogenesis. In the present study, 20 fecal samples were collected by written consent from COVID-19 patients. According to the manufacturer's protocol, virus nucleic acid was extracted from stool samples and the SARS-CoV-2 genome presence in stool samples was confirmed by RT-PCR assay. Three viral genes, S, nsp12, and nsp2, were amplified using the reverse transcription polymerase chain reaction (RT-PCR) method and specific primers. Multiple sequencing alignment (MSA) was performed in the CLC word bench, and a phylogenetic tree was generated by MEGA X based on the neighbor-joining method. Of all cases, 11 (55%) were males. The mean age of the patients was 33.6 years. Diabetes (70%) and blood pressure (55%) were the most prevalent comorbidities. All 20 patients were positive for SARS-CoV-2 infection in respiratory samples. Molecular analysis investigation among 20 stool samples revealed that the SARS-CoV-2 genome was found among 10 stool samples; only three samples were used for sequencing. The polymorphism and phylogenetic analysis in SARS-CoV-2 showed great similarity among all of the evaluated genes with the Wuhan reference sequence and all of the current variants of concern (VOCs). The current study represents a great similarity in polymorphism and phylogenetic analysis of the SARS-CoV-2 isolates with the Wuhan reference sequence and all of the current VOC in the particular evaluated partial sequences of S, nsp12, and nsp2.

Age-Specific Changes in Virulence Associated With Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Variants of Concern.

BACKGROUND: Novel variants of concern (VOCs) have been associated with both increased infectivity and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The virulence of SARS-CoV-2 is closely linked to age. Whether relative increases in virulence of novel VOCs are similar across the age spectrum or are limited to some age groups is unknown. METHODS: We created a retrospective cohort of people in Ontario, Canada, who tested positive for SARS-CoV-2 and were screened for VOCs (n = 259 984) between 7 February 2021 and 31 October 2021. Cases were classified as N501Y-positive VOC, probable Delta VOC, or VOC undetected. We constructed age-specific logistic regression models to evaluate associations between N501Y-postive or Delta VOC infections and infection severity using hospitalization, intensive care unit (ICU) admission, and death as outcome variables. Models were adjusted for sex, comorbidity, vaccination status, and temporal trends. RESULTS: Infection with either N501Y-positive or Delta VOCs was associated with significant elevations in risk of hospitalization, ICU admission, and death across age groups compared with infections where a VOC was not detected. The Delta VOC increased hospitalization risk in children aged <10 years by a factor of 2.5 (adjusted odds ratio; 95% confidence interval, 1.3 to 5.0) compared with non-VOCs. There was a significant inverse relationship between age and relative increase in risk of death with the Delta VOC, with younger age groups showing a greater relative increase in risk of death than older individuals. CONCLUSIONS: SARS-CoV-2 VOCs appear to be associated with increased relative virulence of infection in all age groups, though low absolute numbers of outcomes in younger individuals make estimates in these groups imprecise.

COVID-19 Variant Detection with a High-Fidelity CRISPR-Cas12 Enzyme.

Laboratory tests for the accurate and rapid identification of SARS-CoV-2 variants can potentially guide the treatment of COVID-19 patients and inform infection control and public health surveillance efforts. Here, we present the development and validation of a rapid COVID-19 variant DETECTR assay incorporating loop-mediated isothermal amplification (LAMP) followed by CRISPR-Cas12 based identification of single nucleotide polymorphism (SNP) mutations in the SARS-CoV-2 spike (S) gene. This assay targets the L452R, E484K/Q/A, and N501Y mutations, at least one of which is found in nearly all major variants. In a comparison of three different Cas12 enzymes, only the newly identified enzyme CasDx1 was able to accurately identify all targeted SNP mutations. An analysis pipeline for CRISPR-based SNP identification from 261 clinical samples yielded a SNP concordance of 97.3% and agreement of 98.9% (258 of 261) for SARS-CoV-2 lineage classification, using SARS-CoV-2 whole-genome sequencing and/or real-time RT-PCR as test comparators. We also showed that detection of the single E484A mutation was necessary and sufficient to accurately identify Omicron from other major circulating variants in patient samples. These findings demonstrate the utility of CRISPR-based DETECTR as a faster and simpler diagnostic method compared with sequencing for SARS-CoV-2 variant identification in clinical and public health laboratories.

Myocardial injury in patients with SARS-CoV-2 pneumonia: Pivotal role of inflammation in COVID-19.

AIMS: Infection by SARS-CoV-2 may result in a systemic disease and a proportion of patients ranging 15%-44% experienced cardiac injury (CI) diagnosed by abnormal troponin levels. The aim of the present study was to analyse the clinical characteristics of a large series of hospitalized patients for COVID-19 in order to identify predisposing and/or protective factors of CI and the outcome. METHODS AND RESULTS: This is an observational, retrospective study on patients hospitalized in two Italian centres (San Raffaele Hospital and Cremona Hospital) for COVID-19 and at least one high-sensitivity cardiac troponin (hs-cTnt) measurement during hospitalization. CI was defined if at least one hs-cTnt value was above the 99th percentile. The primary end-point was the occurrence of CI during hospitalization. We included 750 patients (median age 67, IQR 56-77 years; 69% males), of whom 46.9% had history of hypertension, 14.7% of chronic coronary disease and 22.3% of chronic kidney disease (CKD). Abnormal troponin levels (median troponin 74, IQR 34-147 ng/l) were detected in 390 patients (52%) during the hospitalization. At multivariable analysis age, CKD, cancer, C-reactive protein (CRP) levels were independently associated with CI. Independent predictors of very high troponin levels were chronic kidney disease and CRP levels. Patients with CI showed higher rate of all-cause mortality (40.0% vs. 9.1%, p = 0.001) compared to those without CI. CONCLUSION: This large, multicentre Italian study confirmed the high prevalence of CI and its prognostic role in hospitalized patients with COVID-19, highlighting the leading role of systemic inflammation for the occurrence of CI.

Highly Potent SARS-CoV-2 Neutralization by Intravenous Immunoglobulins manufactured from Post-COVID-19 and COVID-19-Vaccinated Plasma Donations.

From September 2020, some immunoglobulin lots from US plasma contained neutralizing antibodies against the newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Paralleled by the increasing numbers of post-coronavirus disease 2019 (COVID-19) donors, immunoglobulin lot antibody positivity increased to 93% by January 2021, at a mean titer of approximately 30 IU/mL. The correlation predicted that anti-SARS-CoV-2 potency would reach 345 IU/mL by July 2021. In addition to post-COVID-19 donors, the rapidly increasing number of plasma donors vaccinated against COVID-19 resulted in a mean antibody titer of >600 IU/mL in July 2021 immunoglobulin lots, with SARS-CoV-2 antibody titers for several lots even higher than those of earlier produced hyperimmune globulin products.

ACE2-based decoy receptors for SARS coronavirus 2.

SARS coronavirus 2 is neutralized by proteins that block receptor-binding sites on spikes that project from the viral envelope. In particular, substantial research investment has advanced monoclonal antibody therapies to the clinic where they have shown partial efficacy in reducing viral burden and hospitalization. An alternative is to use the host entry receptor, angiotensin-converting enzyme 2 (ACE2), as a soluble decoy that broadly blocks SARS-associated coronaviruses with limited potential for viral escape. Here, we summarize efforts to engineer higher affinity variants of soluble ACE2 that rival the potency of affinity-matured antibodies. Strategies have also been used to increase the valency of ACE2 decoys for avid spike interactions and to improve pharmacokinetics via IgG fusions. Finally, the intrinsic catalytic activity of ACE2 for the turnover of the vasoconstrictor angiotensin II may directly address COVID-19 symptoms and protect against lung and cardiovascular injury, conferring dual mechanisms of action unachievable by monoclonal antibodies. Soluble ACE2 derivatives therefore have the potential to be next generation therapeutics for addressing the immediate needs of the current pandemic and possible future outbreaks.

Evaluation of a SARS-CoV-2 Surrogate Virus Neutralization Test for Detection of Antibody in Human, Canine, Cat, and Hamster Sera.

Surrogate neutralization assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be done without biosafety level 3 containment and in multiple species are desirable. We evaluate a recently developed surrogate virus neutralization test (sVNT) in comparison to 90% plaque reduction neutralization tests (PRNT90) in human, canine, cat, and hamster sera. With PRNT90 as the reference, sVNT had sensitivity of 98.9% and specificity of 98.8%. Using a panel of immune sera corresponding to other coronaviruses, we confirm the lack of cross-reactivity to other coronaviruses in SARS-CoV-2 sVNT and PRNT90, except for cross-reactivity to SARS-CoV-1 in sVNT.

COVID-19 associated with severe autoimmune hemolytic anemia.

BACKGROUND: Autoimmune hemolytic anemia (AIHA) has many known disease associations, including autoimmune, lymphoproliferative, and certain infectious diseases, as well as various medications. Studies have found that severe cases of coronavirus disease 2019 (COVID-19) may be associated with coagulopathies; however, the potential association with AIHA is not clear. CASE REPORT: A patient with no known risk factors or underlying predisposition for developing AIHA presented to a hospital with vague symptoms and profound anemia with a complicated blood bank evaluation. She was found to have COVID-19 and AIHA, for which extensive laboratory testing was performed, including direct antiglobulin tests, elution studies, and cold agglutinin titers, to identify the causative autoantibody. She required multiple blood transfusions and therapeutic interventions before clinical stabilization. DISCUSSION: AIHA is a complex disease with a spectrum of presentations and clinical severity. Many diseases have been associated with a propensity for developing AIHA; however, there are few cases in the literature of patients with COVID-19 and AIHA. Most of the reports involve patients with other underlying conditions that are known to be associated with the development of AIHA. The presentation, clinical findings, and therapeutic interventions in a patient with severe AIHA, without other underlying conditions, in the setting of COVID-19 are discussed. CONCLUSIONS: There are few reports of patients with concurrent COVID-19 and AIHA, and the association is not clear. Although COVID-19 has been shown to be associated with coagulopathies, more research is required to determine whether AIHA may also be a potential complication.

Aging and diabetes drive the COVID-19 forwards; unveiling nature and existing therapies for the treatment.

Human SARS Coronavirus-2 (SARS-CoV-2) has infected more than 170 million people worldwide and resulted in more than 3.5 million deaths so far. The infection causes Coronavirus disease (COVID-19) in people of all age groups, notably diabetic and old age people, at a higher risk of infectivity and fatality. Around 35% of the patients who have died of the disease were diabetic. The infection is associated with weakening immune response, chronic inflammation, and potential direct pancreatic impairment. There seems to be a three-way association of the SARS-CoV-2 infection with diabetes and aging. The COVID-19 infection causes metabolism complications, which may induce diabetes and accelerate aging in healthy individuals. How does diabetes elevate the likelihood of the infection is not clearly understood. we summarize mechanisms of accelerated aging in COVID-19 and diabetes, and the possible correlation of these three diseases. Various drug candidates under different stages of pre-clinical or clinical developments give us hope for the development of COVID-19 therapeutics, but there is no approved drug so far to treat this disease. Here, we explored the potential of anti-diabetic and anti-aging natural compounds for the COVID-19 treatment. We have also reviewed different therapeutic strategies with plant-based natural products that may be used to cure patients infected with SARS-CoV-2 and post-infection syndrome.

Evaluation of different platforms for the detection of anti-SARS coronavirus-2 antibodies, Thailand.

BACKGROUND: Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) help determine previous infection in individuals, regardless of whether they are asymptomatic or symptomatic. The detection of antibodies serves several purposes, including supporting other assays for disease diagnosis, conducting seroepidemiological studies, and evaluating vaccines. Many platforms of immunological methods for anti-SARS-CoV-2 antibody detection and their performance require validation. METHODS: This study evaluated the test performance of three autoanalyzer-based assays (Architect IgG, Vitros IgG, and Vitros total Ig) and one manual ELISA (Wantai total Ig) against a microneutralization (microNT) assay on the detection of SARS-CoV-2 antibodies. Furthermore, an indirect immunofluorescence assay verified the discordant results between the microNT and commercial assays. The test sensitivity, specificity, positive predictive value, and negative predictive value were determined based on four groups of 1005 serum samples: 102 COVID-19 prepandemic sera, 45 anti-SARS-CoV-2 positive sera, 366 sera of people at risk, and 492 sera of citizens returning from countries with a high prevalence of infection. RESULTS: The analyses as a whole showed that the performance of these commercial assays was comparable. Each group was also analysed separately to gain further insight into test performance. The Architect did not detect two positive sera of people at risk (prevalence of infection 0.55%). The other methods correctly identified these two positive sera but yielded varying false-positive results. The group of returning travellers with an infection rate of 28.3% (139 of 492) better differentiated the test performance of individual assays. CONCLUSIONS: High-throughput Architect and Vitros autoanalyzers appear appropriate for working on large sample sizes in countries that can afford the cost. The Wantai ELISA, while requiring more individual time and technical skill, may provide reliable results at a lower cost. The selection of assays will depend on the laboratory facilities and feasibility.

Assessment of the HScore as a predictor of disease outcome in patients with COVID-19.

Severe coronavirus disease 2019 (COVID-19) accompanies hypercytokinemia, similar to secondary hemophagocytic lymphohistiocytosis (sHLH). We aimed to find if HScore could predict disease severity in COVID-19. HScore was calculated in hospitalized children and adult patients with a proven diagnosis of COVID-19. The need for intensive care unit (ICU), hospital length of stay (LOS), and in-hospital mortality were recorded. The median HScore was 43.0 (IQR 0.0-63.0), which was higher in those who needed ICU care (59.7, 95% CI 46.4-72.7) compared to those admitted to non-ICU medical wards (38.8, 95% CI 32.2-45.4; P = 0.003). It was also significantly higher in patients who died of COVID-19 (105.1, 95% CI 53.7-156.5) than individuals who survived (41.5, 95% CI 35.8-47.1; P = 0.005). Multivariable logistic regression analysis revealed that higher HScore was associated with a higher risk of ICU admission (adjusted OR = 4.93, 95% CI 1.5-16.17, P = 0.008). The risk of death increased by 20% for every ten units increase in HScore (adjusted OR 1.02, 95% CI 1.00-1.04, P = 0.009). Time to discharge was statistically longer in high HScore levels than low levels (HR = 0.41, 95% CI 0.24-0.69). HScore is much lower in patients with severe COVID-19 than sHLH. Higher HScore is associated with more ICU admission, more extended hospitalization, and a higher mortality rate. A modified HScore with a new cut-off seems more practical in predicting disease severity in patients with severe COVID-19.

Do SARS-CoV-2 Infection (COVID-19) and the Medications Administered for Its Treatment Impair Testicular Functions?

PURPOSE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted primarily via respiratory droplets and enters host cells through angiotensin-converting enzyme 2 (ACE-2) receptors. ACE-2 receptors have been identified in many tissues including testes. The aim of the study has been to investigate the long-term effects of SARS-CoV-2 infection (COVID-19) and its relative treatment on male reproductive health. METHODS: Cross-sectional analysis has been performed on 49 recovered COVID-19 patients who had semen analysis prior to the COVID-19 pandemic. Those who had a recovery time lag of at least 3 months have been re-examined, and 29 eligible patients with no andrological problems have been enrolled in the study. Following a detailed physical examination and retrieval of medical history, the values of semen analysis and serum sex hormone parameters have been collected and compared before and after COVID-19 infection. The p value of <0.05 has been considered significant. RESULTS: The average age of the 29 patients has been 31.21 ± 5.48 (range: 18-41) years. Favipiravir has been co-administered with hydroxychloroquine in 17 patients, while the remaining 12 received favipiravir treatment without hydroxychloroquine. The average time between clinical recovery from COVID-19 and collection of semen has been 4.52 ± 1.36 (range: 3-8) months. Before and after COVID-19, serum follicle-stimulating hormone, luteinizing hormone, total testosterone, and prolactin levels, as well as all semen parameters, have been comparable. CONCLUSION: Our study demonstrated that COVID-19 and its treatment with favipiravir and hydroxychloroquine did not affect spermatogenesis and serum androgen levels in the long-term period. Further clinical studies with larger sample size are needed to confirm and support our findings.

Establishing an Analogue Based In Silico Pipeline in the Pursuit of Novel Inhibitory Scaffolds against the SARS Coronavirus 2 Papain-Like Protease.

The ongoing coronavirus pandemic has been a burden on the worldwide population, with mass fatalities and devastating socioeconomic consequences. It has particularly drawn attention to the lack of approved small-molecule drugs to inhibit SARS coronaviruses. Importantly, lessons learned from the SARS outbreak of 2002-2004, caused by severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1), can be applied to current drug discovery ventures. SARS-CoV-1 and SARS-CoV-2 both possess two cysteine proteases, the main protease (Mpro) and the papain-like protease (PLpro), which play a significant role in facilitating viral replication, and are important drug targets. The non-covalent inhibitor, GRL-0617, which was found to inhibit replication of SARS-CoV-1, and more recently SARS-CoV-2, is the only PLpro inhibitor co-crystallised with the recently solved SARS-CoV-2 PLpro crystal structure. Therefore, the GRL-0617 structural template and pharmacophore features are instrumental in the design and development of more potent PLpro inhibitors. In this work, we conducted scaffold hopping using GRL-0617 as a reference to screen over 339,000 ligands in the chemical space using the ChemDiv, MayBridge, and Enamine screening libraries. Twenty-four distinct scaffolds with structural and electrostatic similarity to GRL-0617 were obtained. These proceeded to molecular docking against PLpro using the AutoDock tools. Of two compounds that showed the most favourable predicted binding affinities to the target site, as well as comparable protein-ligand interactions to GRL-0617, one was chosen for further analogue-based work. Twenty-seven analogues of this compound were further docked against the PLpro, which resulted in two additional hits with promising docking profiles. Our in silico pipeline consisted of an integrative four-step approach: (1) ligand-based virtual screening (scaffold-hopping), (2) molecular docking, (3) an analogue search, and, (4) evaluation of scaffold drug-likeness, to identify promising scaffolds and eliminate those with undesirable properties. Overall, we present four novel, and lipophilic, scaffolds obtained from an exhaustive search of diverse and uncharted regions of chemical space, which may be further explored in vitro through structure-activity relationship (SAR) studies in the search for more potent inhibitors. Furthermore, these scaffolds were predicted to have fewer off-target interactions than GRL-0617. Lastly, to our knowledge, this work contains the largest ligand-based virtual screen performed against GRL-0617.

Clinical Outcomes in 55 Patients With Severe Acute Respiratory Syndrome Coronavirus 2 Who Were Asymptomatic at Hospital Admission in Shenzhen, China.

An epidemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread unexpectedly in Wuhan, Hubei Province, China, since December 2019. There are few reports about asymptomatic contacts of infected patients identified as positive for SARS-CoV-2 through screening. We studied the epidemiological and clinical outcomes in 55 asymptomatic carriers who were laboratory confirmed to be positive for SARS-CoV-2 through nucleic acid testing of pharyngeal swab samples. The asymptomatic carriers seldom occurred among young people (aged 18-29 years) who had close contact with infected family members. In the majority of patients, the outcome was mild or ordinary 2019 novel coronavirus disease during hospitalization.

No SARS-CoV-2 Neutralization by Intravenous Immunoglobulins Produced From Plasma Collected Before the 2020 Pandemic.

The 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing, antibodies to the new species in humans is unclear. The question is particularly relevant for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment. Testing 54 intravenous immunoglobulin preparations, produced from plasma collected in Europe and the United States, confirmed highly potent neutralization of a seasonal coronavirus; however, no cross-neutralization of the new SARS-CoV-2 was seen.

Associations of Early COVID-19 Cases in San Francisco With Domestic and International Travel.

In early-to-mid March 2020, 20 of 46 (43%) COVID-19 cases at a tertiary care hospital in San Francisco, California were travel related. Cases were significantly associated with travel to either Europe (odds ratio, 6.1) or New York (odds ratio, 32.9). Viral genomes recovered from 9 of 12 (75%) cases co-clustered with lineages circulating in Europe.

Deep mutagenesis in the study of COVID-19: a technical overview for the proteomics community.

INTRODUCTION: The spike (S) of SARS coronavirus 2 (SARS-CoV-2) engages angiotensin-converting enzyme 2 (ACE2) on a host cell to trigger viral-cell membrane fusion and infection. The extracellular region of ACE2 can be administered as a soluble decoy to compete for binding sites on the receptor-binding domain (RBD) of S, but it has only moderate affinity and efficacy. The RBD, which is targeted by neutralizing antibodies, may also change and adapt through mutation as SARS-CoV-2 becomes endemic, posing challenges for therapeutic and vaccine development. AREAS COVERED: Deep mutagenesis is a Big Data approach to characterizing sequence variants. A deep mutational scan of ACE2 expressed on human cells identified mutations that increase S affinity and guided the engineering of a potent and broad soluble receptor decoy. A deep mutational scan of the RBD displayed on the surface of yeast has revealed residues tolerant of mutational changes that may act as a source for drug resistance and antigenic drift. EXPERT OPINION: Deep mutagenesis requires a selection of diverse sequence variants; an in vitro evolution experiment that is tracked with next-generation sequencing. The choice of expression system, diversity of the variant library and selection strategy have important consequences for data quality and interpretation.

Anesthesia for oral surgeries during the COVID-19 pandemic.

The severe acute respiratory syndrome corona virus 2(SARS-Cov2) virus replicates in the nasal cavity, nasopharynx, and the oropharynx. During oral surgery, the risk of viral transmission is high during instrumentation in these areas, while performing airway management procedures, the oral surgery itself, and related procedures. During the corona virus disease 2019 (COVID-19) pandemic, patients with an oral pathology usually present for emergency procedures. However, patients with oral cancer, being a semi-emergency, may also present for diagnostic and therapeutic procedures. When elective surgeries are resumed, these patients will come to the operating room. In asymptomatic patients, the false-negative rate can be as high as 30%. These patients are a source of infection to the healthcare workers and other patients. This mandates universal precautions to be taken for all patients presenting for surgery. Lesions along the airway, distorted anatomy secondary to cancer therapy, shared airway with the surgeon, surgical handling of the airway and the risk of bleeding, make airway management challenging in these patients, especially while wearing personal protective equipment. Airway management procedures, oral surgery, use of cautery, and other powered surgical instruments in the aero digestive tract, along with constant suctioning are a source of significant aerosol generation, further adding to the risk of viral transmission. Maintaining patient safety, while protecting the healthcare workers from getting infected during oral surgery is paramount. Meticulous advance planning and team preparation are essential. In this review, we discuss the challenges and recommendations for safe anesthesia practice for oral surgery during the COVID-19 pandemic, with special emphasis on risk mitigation.