Long-COVID and Post-COVID Health Complications: An Up-to-Date Review on Clinical Conditions and Their Possible Molecular Mechanisms

The COVID-19 pandemic has infected millions worldwide, leaving a global burden for long-term care of COVID-19 survivors. It is thus imperative to study post-COVID (i.e., short-term) and long-COVID (i.e., long-term) effects, specifically as local and systemic pathophysiological outcomes of other coronavirus-related diseases (such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS)) were well-cataloged. We conducted a comprehensive review of adverse post-COVID health outcomes and potential long-COVID effects. We observed that such adverse outcomes were not localized. Rather, they affected different human systems, including: (i) immune system (e.g., Guillain–Barré syndrome, rheumatoid arthritis, pediatric inflammatory multisystem syndromes such as Kawasaki disease), (ii) hematological system (vascular hemostasis, blood coagulation), (iii) pulmonary system (respiratory failure, pulmonary thromboembolism, pulmonary embolism, pneumonia, pulmonary vascular damage, pulmonary fibrosis), (iv) cardiovascular system (myocardial hypertrophy, coronary artery atherosclerosis, focal myocardial fibrosis, acute myocardial infarction, cardiac hypertrophy), (v) gastrointestinal, hepatic, and renal systems (diarrhea, nausea/vomiting, abdominal pain, anorexia, acid reflux, gastrointestinal hemorrhage, lack of appetite/constipation), (vi) skeletomuscular system (immune-mediated skin diseases, psoriasis, lupus), (vii) nervous system (loss of taste/smell/hearing, headaches, spasms, convulsions, confusion, visual impairment, nerve pain, dizziness, impaired consciousness, nausea/vomiting, hemiplegia, ataxia, stroke, cerebral hemorrhage), (viii) mental health (stress, depression and anxiety). We additionally hypothesized mechanisms of action by investigating possible molecular mechanisms associated with these disease outcomes/symptoms. Overall, the COVID-19 pathology is still characterized by cytokine storm that results to endothelial inflammation, microvascular thrombosis, and multiple organ failures.     

Potential Molecular Mechanisms of Rare Anti-Tumor Immune Response by SARS-CoV-2 in Isolated Cases of Lymphomas

Recently, two cases of complete remission of classical Hodgkin lymphoma (cHL) and follicular lymphoma (FL) after SARS-CoV-2 infection were reported. However, the precise molecular mechanism of this rare event is yet to be understood. Here, we hypothesize a potential anti-tumor immune response of SARS-CoV-2 and based on a computational approach show that: (i) SARS-CoV-2 Spike-RBD may bind to the extracellular domains of CD15, CD27, CD45, and CD152 receptors of cHL or FL and may directly inhibit cell proliferation. (ii) Alternately, upon internalization after binding to these CD molecules, the SARS-CoV-2 membrane (M) protein and ORF3a may bind to gamma-tubulin complex component 3 (GCP3) at its tubulin gamma-1 chain (TUBG1) binding site. (iii) The M protein may also interact with TUBG1, blocking its binding to GCP3. (iv) Both the M and ORF3a proteins may render the GCP2-GCP3 lateral binding where the M protein possibly interacts with GCP2 at its GCP3 binding site and the ORF3a protein to GCP3 at its GCP2 interacting residues. (v) Interactions of the M and ORF3a proteins with these gamma-tubulin ring complex components potentially block the initial process of microtubule nucleation, leading to cell-cycle arrest and apoptosis. (vi) The Spike-RBD may also interact with and block PD-1 signaling similar to pembrolizumab and nivolumab- like monoclonal antibodies and may induce B-cell apoptosis and remission. (vii) Finally, the TRADD interacting “PVQLSY” motif of Epstein-Barr virus LMP-1, that is responsible for NF-kB mediated oncogenesis, potentially interacts with SARS-CoV-2 M^pro, NSP7, NSP10, and spike (S) proteins, and may inhibit the LMP-1 mediated cell proliferation. Taken together, our results suggest a possible therapeutic potential of SARS-CoV-2 in lymphoproliferative disorders.     

Lateral rectus dermoid cyst presenting as incomitant esotropia

A 24-year-old male presented with decreased vision associated with inward deviation of his left eye since childhood and gradually progressive prominence of left eye for 6 months. Left eye examination revealed visual acuity of 2/60, convergent squint with restricted abduction and medial dystopia. Computed tomography (CT) scan showed a well-circumscribed mass with fat fluid levels temporal to the optic nerve indistinguishable from the left lateral rectus. Intraoperatively, a well-encapsulated mass was identified within the lateral rectus muscle which was confirmed as dermoid cyst on histopathology. Patient subsequently underwent surgical correction of his esotropia and the final cosmetic outcome was satisfactory. Dermoid cysts are common orbital lesions usually found overlying suture lines. A dermoid cyst presenting within the ocular muscles is a rare entity. Deep dermoid cyst should be considered as one of the differentials for focal enlargement of extraocular muscles.     

Safety and Efficacy of Intravitreal Dexamethasone Implant for Refractory Uveitic Macular Edema in Adults and Children

Purpose: To assess safety and efficacy of intravitreal dexamethasone (DEX) implant in refractory uveitic macular edema (ME).

Methods: We retrospectively analyzed medical records of patients with nonresponsive ME secondary to chronic, noninfectious intermediate or posterior uveitis, treated with intravitreal DEX implants.

Results: A total of 42 eyes of 34 patients (aged 6–67 years) received 56 implants. Mean follow-up was 19.2 ± 2.2 months after DEX implant. The mean visual acuity (0.48 ± 0.06 logMAR to 0.34 ± 0.1 logMAR) and mean central retinal thickness (472.2 ± 35 to 274.7 ± 60.6 µm) improved considerably before and after DEX implant. A total of 11 eyes needed repeat implants after a prolonged time to recurrence (12.6–20.9 months). A total of 10 eyes needed no additional treatment. Oral steroids could be stopped in 40% patients. Intraocular pressure increased in seven and cataract progressed in six eyes.

Conclusion: Intravitreal DEX implant is safe and effective adjunct therapy. It reduces dependence on systemic steroids, immunosuppressives and provides long-term effects.     

Microrna let-7: an emerging next-generation cancer therapeutic

In recent years, various rna-based technologies have been under evaluation as potential next-generation cancer therapeutics. Micrornas (mirnas), known to regulate the cell cycle and development, are deregulated in various cancers. Thus, they might serve as good targets or candidates in an exploration of anticancer therapeutics. One attractive candidate for this purpose is let-7 (“lethal-7”).Let-7 is underexpressed in various cancers, and restoration of its normal expression is found to inhibit cancer growth by targeting various oncogenes and inhibiting key regulators of several mitogenic pathways. In vivo, let-7 administration was found effective against mouse-model lung and breast cancers, and our computational prediction supports the possible effectiveness of let-7 in estrogen receptor (er)–positive metastatic breast cancer. Data also suggest that let-7 regulates apoptosis and cancer stem cell (csc) differentiation and can therefore be tested as a potential therapeutic in cancer treatment. However, the exact role of let-7 in cancer is not yet fully understood. There is a need to understand the causative molecular basis of let-7 alterations in cancer and to develop proper delivery systems before proceeding to therapeutic applications. This article attempts to highlight certain critical aspects of let-7’s therapeutic potential in cancer.     

The addictive brain: all roads lead to dopamine

This article will touch on theories, scientific research and conjecture about the evolutionary genetics of the brain function and the impact of genetic variants called polymorphisms on drug-seeking behavior. It will cover the neurological basis of pleasure-seeking and addiction, which affects multitudes in a global atmosphere where people are seeking "pleasure states".