NMDA Receptor Modulation in COVID-19-Associated Acute Respiratory Syndrome in both In Silico and In Vitro Approach.

The normal function of the N-methyl D-aspartate receptors (NMDAR) in human lungs depends on precisely regulated synaptic glutamate levels. Pathophysiology of the lungs is brought on by the changes in homeostasis of glutamate in the synapsis that leads to abnormal NMDAR activity. Severe acute respiratory syndrome (SARS) primarily results in lung infections, particularly lung muscle stiffening, and NMDA receptor potentiation may increase calcium ion influx and support downstream signaling mechanisms. Hence, NMDAR modulators that depend on glutamate levels could be therapeutically useful medications with fewer unintended side effects. A compound called THP (tetrahydropalmatine) that amplifies Ca2+ influx and potentiates NMDA receptors has been identified in the current study. In asthmatic human airway smooth muscle (HASM) cells, THP regulates the NMDA receptor and helps in asthmatic ASM contraction, and the pharmacological stimulation of ASM depends on both brain and respiratory NMDA receptors. Glutamate potency is altered by this substance without any voltage-dependent side effects. Additionally, a GGPP (geranylgeranyl pyrophosphate)-dependent mechanism of THP reduced the production of pro-inflammatory cytokines in ASM. THP is distinctive in terms of its chemical makeup, functioning, and agonist concentration-dependent and allosteric modulatory activity. To treat COVID-19-related SARS, THP, or any future-related compounds will make good drug-like molecule candidates.

Relation between Guillain-Barré syndrome and Covid-19: Case-Series.

Approximately two-thirds of the Guillain-Barré syndrome (GBS) cases are preceded by upper respiratory tract infection or enteritis. There has been previous documentation of a clear association between Covid-19 and GBS. Covid-19 can affect the nervous tissue either through direct damage or through triggering a host immune response with subsequent development of autoimmune diseases such as GBS. Covid-19 can affect the host`s immune system through the activation and interaction of the T-and B-lymphocytes with subsequent production of antibodies that cross-react with the gangliosides. Depending on the nature of the neuronal autoimmune destruction, the affected individual may have either a demyelinating or axonal subtype of GBS. These subtypes differ not only in symptoms but also in the likelihood of recovery. This report presents two cases of GBS that developed after the respiratory symptoms of Covid-19. Their neurological features indicated demyelination, axonal damage, irritation of spinal nerve roots, and impaired sensory and motor transmission with additional facial nerve palsy in the second-studied case. This case report highlights the relationship between GBS and Covid-19 infection.

Inhibition of SARS-CoV-2 nucleocapsid protein-RNA interaction by guanosine oligomeric RNA.

The interaction of the ß-coronavirus severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) nucleocapsid (N) protein with genomic RNA is initiated by specific RNA regions and subsequently induces the formation of a continuous polymer with characteristic structural units for viral formation. We hypothesized that oligomeric RNAs, whose sequences are absent in the 29.9-kb genome sequence of SARS-CoV-2, might affect RNA-N protein interactions. We identified two such hexameric RNAs, In-1 (CCGGCG) and G6 (GGGGGG), and investigated their effects on the small filamentous/droplet-like structures (< a few µm) of N protein-genomic RNA formed by liquid-liquid phase separation. The small N protein structures were sequence-specifically enhanced by In-1, whereas G6 caused them to coalesce into large droplets. Moreover, we found that a guanosine 12-mer (G12, GGGGGGGGGGGG) expelled preexisting genomic RNA from the small N protein structures. The presence of G12 with the genomic RNA suppressed the formation of the small N protein structures, and alternatively apparently altered phase separation to induce the formation of large droplets with unclear phase boundaries. We showed that the N-terminal RNA-binding domain is required for the stability of the small N protein structures. Our results suggest that G12 may be a strong inhibitor of the RNA-N protein interaction.

Chinese pregnant women's knowledge, attitude, and practice of self-protection against coronavirus disease 2019 during the post-pandemic period: A structural equation modeling-based survey.

This study aimed to investigate the Chinese pregnant women's levels of knowledge, attitude, and practice (KAP) of self-protection against coronavirus disease 2019 (COVID-19) during the post-pandemic period, to aid the development of targeted health education. An online questionnaire was conducted for 2156 Chinese pregnant women from October 1, 2021, to December 31, 2021, to collect socio-demographic and KAP information. Structural equation modeling (SEM) was used to determine self-protection-related factors. The mean age of the participants was 30 ± 4.1 years. SEM indicated that pregnant women's level of knowledge can directly and indirectly affect the practice of self-protection (r = 0.23) through their belief, with a correlation coefficient of 0.56 and 0.46 between knowledge and belief and belief and practice, respectively. The "basic protection" and "hospital visits after infection" exerted the greatest impact on knowledge formation, with correlation coefficients of 0.85 and 0.89, respectively. Attitude had a direct effect on practice with a correlation coefficient of 0.46. "Awareness of prevention and control" and "family and social support" had the greatest impact on belief formation, with correlation coefficients of 0.77 and 0.73, respectively. Pregnant Chinese women were generally familiar with COVID-19 knowledge, and their levels of knowledge and beliefs particularly affect the practice of self-protection. Health education aimed at improving pregnant women's knowledge and belief toward self-protection against COVID-19 may be an effective way to guide them toward positive practices and promote their health and that of their babies.

Assessing psychometric challenges and fatigue during the COVID-19 pandemic.

Environmental hazards and/or pandemics may push humans to use different protective methods to maintain their well-being. This study aimed to identify populations vulnerable to psychometric challenges and fatigue during the Coronavirus Disease (COVID-19) pandemic in Kazakhstan. A total of 1,592 participants were recruited and asked to complete the Multidimensional Fatigue Inventory-20 (MFI-20). Participants were classified according to gender and age. Data were analyzed using the Chi-square test (x2) and MedCalc to detect the odds of MFI-scales with a score ≥12 in women compared to men. Young women had significantly higher odds (OR) of reduced activity (OR 2.4, p<0.0001), physical (OR 2.5, p<0.0001), and mental fatigue (OR 3.4, p<0.0001) than young men. Middle-aged women had significantly higher odds of general fatigue (OR 2.1; p<0.0001), reduced motivation (OR 2.1, p<0.0001), physical (OR 2.1, p<0.0001), and mental fatigue (OR 1.9, p<0.0001) than did middle-aged men. Elderly women had significantly higher odds of general fatigue (OR 3.6, p<0.0001), reduced motivation (OR 3.5, p<0.0001), and physical fatigue (OR 3.5, p<0.0001) than men in the same age category. The study highlights that women were more susceptible, with significantly increased odds of experiencing various aspects of fatigue syndrome compared to men during the COVID-19 pandemic in Kazakhstan. Therefore, it is necessary to investigate individual behavioral changes to help identify vulnerable populations and provide relevant evidence for developing protocols and guidelines during pandemics and/or outbreaks.

Equipment-free, salt-mediated immobilization of nucleic acids for nucleic acid lateral flow assays.

As the world has been facing several deadly virus crises, including Zika virus disease, Ebola virus disease, severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and Coronavirus disease 2019 (COVID-19), lateral flow assays (LFAs), which require minimal equipment for point-of-care of viral infectious diseases, are garnering much attention. Accordingly, there is an increasing demand to reduce the time and cost required for manufacturing LFAs. The current study introduces an equipment-free method of salt-mediated immobilization of nucleic acids (SAIoNs) for LFAs. Compared to general DNA immobilization methods such as streptavidin-biotin, UV-irradiation, and heat treatment, our method does not require special equipment (e.g., centrifuge, UV-crosslinker, heating device); therefore, it can be applied in a resource-limited environment with reduced production costs. The immobilization process was streamlined and completed within 30 min. Our method improved the color intensity signal approximately 14 times compared to the method without using SAIoNs and exhibited reproducibility with the long-term storage stability. The proposed method can be used to detect practical targets (e.g., SARS-CoV-2) and facilitates highly sensitive and selective detection of target nucleic acids with multiplexing capability and without any cross-reactivity. This novel immobilization strategy provides a basis for easily and inexpensively developing nucleic acid LFAs combined with various types of nucleic acid amplification.

Invasive fungal sinusitis-A neglected but important association with COVID 19 infection and a ticking bomb.

A retrospective analysis of severe acute respiratory syndrome (SARS) and influenza data worldwide has concluded that fungal coinfections associated with global SARS-coronavirus 2 (CoV-2) are likely to be missed or misdiagnosed. The coronavirus disease-2019 (COVID)-19 patients, especially those who are severely ill or immunocompromised, are more likely to suffer from invasive mycoses which require early detection and treatment. We report two such cases, one of which is a case of aspergillosis of unilateral orbit and maxilla and another case is of mucormycosis infection of the paranasal sinuses and bilateral orbits.

Complex Hallucinations in Hospitalized Rehabilitation Patients With COVID-19.

Objectives: To explore the characteristics of hallucinations in hospitalized rehabilitation patients with COVID-19. Design: Retrospective review using medical records of patients with COVID-19 and admitted to the acute inpatient rehabilitation unit (ARU). Setting: A public hospital in southern California, specializing in rehabilitation medicine. Participants: Patients with COVID-19 and hallucinations who were consecutively admitted from January 1st to April 30th, 2021. Interventions: Not applicable. Main Outcome Measures: Types and themes of hallucinations. Results: Eight of the 37 patients (21.6%) admitted to the ARU with COVID-19 exhibited hallucinations. All were Hispanic and 7 of them were men; their average age was 56.5 (range: 38-71). Seven patients had COVID-19 pneumonia and 1 developed respiratory distress secondary to Guillain-Barre Syndrome. One patient had posterior reversible encephalopathy syndrome. The average length of stay in the intensive care unit (ICU) was 31.3 days (range: 8-48). Most of the hallucinations occurred during their ICU stay and 2 continued to their ARU stay. All recalled details of hallucinations with 7 exhibiting visual hallucinations, consistent with peduncular hallucinosis with or without auditory and/or tactile components. One patient experienced tactile hallucinations. The themes of hallucinations identified to reflect the contents of the hallucinations were patients' comfort-seeking, fearfulness, and seeing deceased family members. All patients had impaired cognition at the ARU admission but improved at discharge. Four patients had depressed mood/anxiety and 1 had depressed mood alone but without a history of psychiatric illness. ICU delirium was documented in 5 patients. The negative experience of hallucinations seemed to affect their participation of the ARU stay. Conclusions: More than 20% of patients with COVID-19 who were transferred to attend inpatient rehabilitation exhibited hallucinations. It remains uncertain if these hallucinations were related to the SARS-CoV-2 infection. Multidisciplinary rehabilitation team should be aware to support patients with COVID-19 who experience hallucinations.

Single domain antibodies derived from ancient animals as broadly neutralizing agents for SARS-CoV-2 and other coronaviruses.

With severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as an emergent human virus since December 2019, the world population is susceptible to coronavirus disease 2019 (COVID-19). SARS-CoV-2 has higher transmissibility than the previous coronaviruses, associated by the ribonucleic acid (RNA) virus nature with high mutation rate, caused SARS-CoV-2 variants to arise while circulating worldwide. Neutralizing antibodies are identified as immediate and direct-acting therapeutic against COVID-19. Single-domain antibodies (sdAbs), as small biomolecules with non-complex structure and intrinsic stability, can acquire antigen-binding capabilities comparable to conventional antibodies, which serve as an attractive neutralizing solution. SARS-CoV-2 spike protein attaches to human angiotensin-converting enzyme 2 (ACE2) receptor on lung epithelial cells to initiate viral infection, serves as potential therapeutic target. sdAbs have shown broad neutralization towards SARS-CoV-2 with various mutations, effectively stop and prevent infection while efficiently block mutational escape. In addition, sdAbs can be developed into multivalent antibodies or inhaled biotherapeutics against COVID-19.