When stem cells meet COVID-19: recent advances, challenges and future perspectives

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory coronavirus 2 is currently spreading throughout the world with a high rate of infection and mortality and poses a huge threat to global public health. COVID-19 primarily manifests as hypoxic respiratory failure and acute respiratory distress syndrome, which can lead to multiple organ failure. Despite advances in the supportive care approaches, there is still a lack of clinically effective therapies, and there is an urgent need to develop novel strategies to fight this disease. Currently, stem cell therapy and stem cell-derived organoid models have received extensive attention as a new treatment and research method for COVID-19. Here, we discuss how stem cells play a role in the battle against COVID-19 and present a systematic review and prospective of the study on stem cell treatment and organoid models of COVID-19, which provides a reference for the effective control of the COVID-19 pandemic worldwide.

Detection of respiratory viruses in cases of porcine respiratory disease in nurseries.

Respiratory disease in weaned pigs is a common problem in the field, with a complex aetiology of both viruses and bacteria. In the present study, we investigated the presence of eleven viruses in nasal swabs collected from nurseries (fifty-five clinical outbreaks) under the suspicion of swine influenza A virus (swIAV) by cough and fever. The other ten viruses included influenza B (IBV) and influenza D viruses (IDV), Porcine reproductive and respiratory syndrome virus (PRRSV), Porcine respiratory coronavirus (PRCV), Porcine cytomegalovirus (PCMV), porcine circoviruses 2 (PCV2), 3 (PCV3) and 4 (PCV), Porcine parainfluenza 1 virus (PPIV1) and Swine orthopneumovirus (SOV). Twenty-nine swIAV-positive cases and twenty-six cases of swIAV-negative respiratory disease were primarily established. IBV, IBD, PCV4 and PPIV1 were not found in any case, while PRCV, SOV, and PCMV were more likely to be found in swIAV-positive nurseries with respiratory disease ( p<0.05) although, globally, PCV3, PRRSV, and PCMV were the most frequently detected agents on herd level. At an individual level, the prevalence of different viruses was: swIAV 48.6%; PRCV 48.0%; PRRSV 31.6%; SOV 33.8%; PCMV 48.3%, PCV2 36.0%; and PCV3 33.0%. Beyond that, it was common to find animals with low Ct values (< 30) for all agents except for PCV2 and PCV3. When analysed the association between different pathogens, PRCV was the one with the most associations. It positively interacted ( p < 0.05) with swIAV and SOV but was negatively associated ( p < 0.05) with PRRSV and PCVM. Besides these, swIAV and PRRSV were negatively related (p < 0.05). Further analysis of suckling pigs showed that circulation of PRCV, PCMV, SOV, and PCV3 started in the maternities, suggesting a role of the sows in the transmission. Overall, our data may contribute to a better understanding of the complex aetiology and the epidemiology of respiratory disease in weaners. This is the first report of SOV in Spain.

SARS-CoV-2 diverges from other betacoronaviruses in only partially activating the IRE1α/XBP1 ER stress pathway in human lung-derived cells

Despite the efficacy of vaccines, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 5 million individuals worldwide and continues to spread in countries where the vaccines are not yet widely available or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed essential for viral replication. We examined the activation status and requirement of the master UPR sensor IRE1α kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1α-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and the murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1α as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1α whereby it autophosphorylates, but its RNase fails to splice XBP1. Moreover, IRE1α was dispensable for optimal replication in human cells for all coronaviruses tested. Our findings demonstrate that IRE1α activation status differs upon infection with distinct betacoronaviruses and is not essential for efficient replication of any of them. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1α through an unknown mechanism, perhaps as a strategy to eliminate detection by the host immune system.

Comparative genomic analysis reveals varying levels of mammalian adaptation to coronavirus infections

Severe acute respiratory coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, is of zoonotic origin. Evolutionary analyses assessing whether coronaviruses similar to SARS-CoV-2 infected ancestral species of modern-day animal hosts could be useful in identifying additional reservoirs of potentially dangerous coronaviruses. We reasoned that if a clade of species has been repeatedly exposed to a virus, then their proteins relevant for viral entry may exhibit adaptations that affect host susceptibility or response. We perform comparative analyses across the mammalian phylogeny of angiotensin-converting enzyme 2 (ACE2), the cellular receptor for SARS-CoV-2, in order to uncover evidence for selection acting at its binding interface with the SARS-CoV-2 spike protein. We uncover that in rodents there is evidence for adaptive amino acid substitutions at positions comprising the ACE2-spike interaction interface, whereas the variation within ACE2 proteins in primates and some other mammalian clades is not consistent with evolutionary adaptations. We also analyze aminopeptidase N (APN), the receptor for the human coronavirus 229E, a virus that causes the common cold, and find evidence for adaptation in primates. Altogether, our results suggest that the rodent and primate lineages may have had ancient exposures to viruses similar to SARS-CoV-2 and HCoV-229E, respectively.

Respiratory Tract Pathogens in the COVID-19 era: Data from a Pediatric Emergency Department

Objective The frequency of coinfections in pediatric Coronavirus disease 2019 (COVID-19) cases and their impact on the clinical course are not fully understood. We aimed to investigate the viral and bacterial respiratory pathogens in children admitted to the pediatric emergency department (PED), their clinical course, and the presence of coinfections during the early months of the COVID-19 pandemic. Methods Clinical, laboratory and radiological findings, viral and bacterial pathogens detected by multiplex polymerase chain reaction (PCR) tests in nasopharyngeal swabs, clinical course, and treatments of all children who were tested for severe acute respiratory coronavirus 2 (SARS-CoV-2) at the PED between March 16 and May 15, 2020, were recorded. SARS-CoV-2 PCR-positive and negative groups were compared. Results Out of 570 patients tested for SARS-CoV-2 during the study period, 43 were found positive (7.5%). Non-SARS-CoV-2 viral pathogens were more common in the SARS-CoV-2 PCR-negative group than the SARS-CoV-2 PCR-positive group (13.2%, n = 68 versus 4.7%, n = 2), but this result was not statistically significant. Leukocyte, neutrophil, lymphocyte, and platelet counts were lower in SARS-CoV-2 PCR-positive group. Bacterial panel positivity was significantly higher in the SARS-CoV-2 PCR-positive group compared with the SARS-CoV-2 PCR-negative group (52%, n = 12 versus 28%, n = 91; p < 0.05). The presence of coinfection did not alter the course of therapy in SARS-CoV-2 PCR-positive cases. Conclusion While viral coinfections were rare, bacterial panel positivity was common in children with COVID-19, but this had not influenced management decisions. The limitations of the tests should be kept in mind while interpreting the results.

Electroceutical fabric lowers zeta potential and eradicates coronavirus infectivity upon contact

Coronavirus with intact infectivity attached to PPE surfaces pose significant threat to the spread of COVID-19. We tested the hypothesis that an electroceutical fabric, generating weak potential difference of 0.5 V, disrupts the infectivity of coronavirus upon contact by destabilizing the electrokinetic properties of the virion. Porcine respiratory coronavirus AR310 particles (105) were placed in direct contact with the fabric for 1 or 5 min. Following one minute of contact, zeta potential of the porcine coronavirus was significantly lowered indicating destabilization of its electrokinetic properties. Size-distribution plot showed appearance of aggregation of the virus. Testing of the cytopathic effects of the virus showed eradication of infectivity as quantitatively assessed by PI-calcein and MTT cell viability tests. This work provides the rationale to consider the studied electroceutical fabric, or other materials with comparable property, as material of choice for the development of PPE in the fight against COVID-19.

Symptom monitoring after coronavirus disease 2019 (COVID-19) vaccination in a large integrated healthcare system: Separating symptoms from severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection

Objective: To describe the incidence of systemic overlap and typical coronavirus disease 2019 (COVID-19) symptoms in healthcare personnel (HCP) following COVID-19 vaccination and association of reported symptoms with diagnosis of severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in the context of public health recommendations regarding work exclusion. Design: This prospective cohort study was conducted between December 16, 2020, and March 14, 2021, with HCP who had received at least 1 dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine. Setting: Large healthcare system in New England. Interventions: HCP were prompted to complete a symptom survey for 3 days after each vaccination. Reported symptoms generated automated guidance regarding symptom management, SARS-CoV-2 testing requirements, and work restrictions. Overlap symptoms (ie, fever, fatigue, myalgias, arthralgias, or headache) were categorized as either lower or higher severity. Typical COVID-19 symptoms included sore throat, cough, nasal congestion or rhinorrhea, shortness of breath, ageusia and anosmia. Results: Among 64,187 HCP, a postvaccination electronic survey had response rates of 83% after dose 1 and 77% after dose 2. Report of ≥3 lower-severity overlap symptoms, ≥1 higher-severity overlap symptoms, or at least 1 typical COVID-19 symptom after dose 1 was associated with increased likelihood of testing positive. HCP with prior COVID-19 infection were significantly more likely to report severe overlap symptoms after dose 1. Conclusions: Reported overlap symptoms were common; however, only report of ≥3 low-severity overlap symptoms, at least 1 higher-severity overlap symptom, or any typical COVID-19 symptom were associated with infection. Work-related restrictions for overlap symptoms should be reconsidered.

Mental Health Issues in Covid 19 Recovered Patients of Lahore, Pakistan

Background: Corona virus belongs to the coronaviridea family. Its variant, the severe acute respiratory coronavirus-2 (SARS-COV-2) is a beta coronavirus causing the current Covid-19 outbreak in humans. This virus not only has pathological effects, but it also affects psychologically. Our study aims to find out the mental changes affecting the COVID recovered patients. Methodology: A cross-sectional study was carried at Central Park Medical College from July 2021- August 2021 to assess the psychological stress and anxiety among COVID-19 recovered patients. Data was collected from 96 COVID-19 recovered patients through a self-designed questionnaire using convenient sampling design. Results: The mean age of the participants was 28.07 + 12.45 SD in years. About 44.8% of the participants were female. Approximately 79% participants were graduated or above. About 52.4% of the participants who were infected from COVID-19 mentioned that they lost their appetite during illness. Nearly 71.4% of the participants mentioned that they were more anxious during the illness. Conclusion: Nearly two third participants had sad feelings. A high percentage of respondents had some level of anxiety. Most of the participants reported sudden and panic attacks after COVID. Many respondents said that they were trying to overcome these mental after affects of COVID.

Cerebral Venous Thrombosis Developing after COVID-19 Vaccination: VITT, VATT, TTS, and More

Despite the huge efforts globally underway for preventing or limiting the spread of severe acute respiratory coronavirus disease 2 (SARS-CoV-2), the coronavirus disease 2019 (COVID-19) pandemic outbreak appears still virtually unstoppable. As for many other infectious diseases, COVID-19 vaccination has now become crucial for limiting viral spread, especially for averting hospitalizations, need for intensive care, and fatal outcome. Nonetheless, as for other vaccines, COVID-19 vaccination is not completely free from side effects. Among the adverse events that have been reported after receiving COVID-19 vaccination, special emphasis has been given to an unexpected number of thrombocytopenic episodes with or without thrombotic complications, especially in recipients of adenovirus-based COVID-19 vaccines. Along with a specific clinical presentation, encompassing “atypical” thrombosis (especially cerebral venous [sinus] thrombosis, CVT) more prevalent in young female subjects, this new syndrome called vaccine-induced thrombocytopenia and thrombosis (VITT) is characterized by, and thereby diagnosed for, the presence of three paradigmatic laboratory abnormalities, i.e., low platelet count (<150 × 109/L), elevated plasma D-dimer levels (>0.5 mg/L), accompanied by a positive test for anti-PF4 (platelet factor 4) antibodies assayed with ELISA (enzyme-linked immunosorbent assay) techniques. Timely identification of these important abnormalities by both clinicians and laboratory professional is essential for early diagnosis and management of VITT, since the outcome of this condition may be fatal in half or even more of effected patients with severe disease. Therefore, this narrative review aims to review here the epidemiology, pathogenesis, clinical, and laboratory characteristics of VITT and other COVID-19 vaccine-associated thrombocytopenias.