COVID-19: Cross Reactive Immunity, Herd Immunity, and Convalescent Serum Therapy

Objective: To present various types of vaccines and viral infections which can induce cross-reactive immunity against COVID-19. In addition, this article discusses the role of herd immunity and convalescent serum therapy in preventing and controlling SARS CoV-2. The study also determined the claims and counterclaims about their protective and therapeutic effects. Method: Non-systematic review was done using different articles done on cross-reactive immunity against COVID-19 through vaccinations, previous infections, herd immunity and the therapeutic effects of convalescence serum. The search was done on the PubMed, Google Scholar, and Science Direct, WHO, Euro-surveillance, CDC databases. Results: Many observational correlational studies reported that BCG decreases the incidence and mortality from COVID-19. Furthermore, homology between the COVID-19 virus and the measles, mumps, and rubella (MMR) viruses was discovered. Few studies suggested the presence of cross-immunity between MMR vaccine and SARS-CoV-2. Similarly, few studies suggested protective effects of Oral Polio Vaccine (OPV) against SARS-CoV-2; since both viruses are positive-single-strand RNA (+ssRNA). Diphtheria, pertussis, and tetanus (DPT) vaccines, particularly those that include inactivated whole pertussis vaccine, might induce B and T cell cross-reactive immunity against SARS-CoV-2. Other vaccines against Streptococcus pneumonia, Haemophilus influenza, and Meningococcal meningitis vaccines are suggested also to induce some immunity against Covid-19. It is hypothesized that infections with other Coronaviruses may cause protection against SARS-CoV-2. However, the studies done on these suggestions were mostly observational that can carry a high chance of inherent biases. There are also claims and counterclaims about the effect of herd immunity and convalescence serum on the prevention and control of Covid-19. So, appropriately designed RCTs are needed to prove or disprove their protective and therapeutic effects. Conclusions: There are claims and counterclaims about the protective effects of different vaccines, previous infections, and herd immunity and regarding the therapeutic effects of convalescence serum. Comparing with other vaccines, BCG was suggested to have the highest cross-reactive epitopes against SARS-Cov-2 virus. MMR, OPV, DPT, Influenza, Pneumococcal and meningococcal vaccines are suggested to protect against Covid-19. Previous infection with other Corona viruses, herd immunity and convalescence serum may play roles in the prevention and control of Covid-19. Many large clinical trials are undergoing nowadays and their results are needed to prove or disprove the cross-immunity related to SARS-CoV-2 and the effect of convalescence serum.

The Principles of Antibody Therapy for Infectious Diseases with Relevance for COVID-19

ABSTRACT Antibody therapies such as convalescent plasma and monoclonal antibodies have emerged as major potential therapeutics for coronavirus disease 2019 (COVID-19). Immunoglobulins differ from conventional antimicrobial agents in that they mediate direct and indirect antimicrobial effects that work in concert with other components of the immune system. The field of infectious diseases pioneered antibody therapies in the first half of the 20th century but largely abandoned them with the arrival of conventional antimicrobial therapy. Consequently, much of the knowledge gained from the historical development and use of immunoglobulins such as serum and convalescent antibody therapies was forgotten; principles and practice governing their use were not taught to new generations of medical practitioners, and further development of this modality stalled. This became apparent during the COVID-19 pandemic in the spring of 2020 when convalescent plasma was initially deployed as salvage therapy in patients with severe disease. In retrospect, this was a stage of disease when it was less likely to be effective. Lessons of the past tell us that antibody therapy is most likely to be effective when used early in respiratory diseases. This article puts forth three principles of antibody therapy, namely, specificity, temporal, and quantitative principles, connoting that antibody efficacy requires the administration of specific antibody, given early in course of disease in sufficient amount. These principles are traced to the history of serum therapy for infectious diseases. The application of the specificity, temporal, and quantitative principles to COVID-19 is discussed in the context of current use of antibody therapy against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

in silico Study Reveals Potential Docking Sites of δ 2-isoxazolines derivates for Inhibiting Russell’s Viper PLA2 Toxin

Snake venom phospholipase A2s (svPLA2s) has been known as the most abundant component and predominant cause of Russell’s viper envenomation. Limitation to serum therapy and considerable pharmacological interest led the researcher to synthesized multi-toxic PLA2 inhibitors, δ2-isoxazolines derivate. Although δ2- isoxazolines derivate already proved inhibitor activity in Group II svPLA2 with known IC50, their mechanism of action remains unveiled. Our recent study investigated their inhibitory activity via molecular docking. The virtual screening revealed that the ligand with diverse structures tied to the relatively same active site region. The result sheds light on the significance of His48 and Asp49 as part of the pro-inflammatory eliciting region. ADME analysis was also performed to filter and identify the best potential inhibitor acceptable for human use. This moiety leads to finding a better therapeutic strategy of svPLA2 inhibitors both as an alternative to serum anti-venom treatment.

Synthesis and Biological Evaluation of Novel 1,3-Benzoxathiol-2-one Sulfonamides against Toxic Activities of the Venom of Bothrops jararaca and B. jararacussu Snakes

This work describes the synthesis of new 1,3-benzoxathiol-2-one sulfonamides and evaluation of their ability to inhibit some in vitro (coagulant, proteolytic and hemolytic) and in vivo (hemorrhagic, edematogenic and lethality) toxic activities of Bothrops jararaca and B. jararacussu venoms. Compounds have been synthesized from the coupling of intermediate 5-amino-6‑methoxybenzo[d] [1,3]oxathiol-2-one 4 with benzenesulfonyl chlorides. Characterization of the products was achieved by nuclear magnetic resonance (NMR) and electrospray ionization mass spectra (ESI-MS) techniques. Biological assay results have shown that most of compounds inhibited the main toxic activities of the venom of the two snake species. Compound 5b (N-(6‑methoxy-2‑oxobenzo[d] [1,3]oxathiol-5-yl)-4-nitrobenzenesulfonamide) was the most efficient in inhibiting hemolysis of B. jararaca, and coagulation and proteolysis induced by both venoms. For in vivo activities, all compounds inhibited the edema, from 35 to 72%, and most of them exhibited antihemorrhagic and antilethality activities. Thus, the results pointed to the biological potential of these compounds, being promising molecules to treat envenomation by these snakes as well as to aid the current antivenom serum therapy.

Autologous serum therapy: a viable option for chronic spontaneous urticaria

<p class="abstract"><strong>Background:</strong> Chronic urticaria (CU) is a common disorder causing decrease in quality of life of patients with associated morbidity, chronic dependence on medications and a huge pill burden. CU is multifactorial and a subset of patients have an autoimmune background for their condition which is confirmed by a positive skin reaction to ASST. This study compared the efficacy of Autologous serum therapy in both ASST positive and ASST negative patients by evaluating total severity score (TSS).</p><p class="abstract"><strong>Methods: </strong>This quasi experimental study was conducted on fifty patients were selected randomly and withdrawn from antihistaminic use. ASST was done for all patients and AST was administered to all patients in both groups for 9 weeks. The patients were followed up at 4 weeks and 12 weeks after completion of AST. TSS measurements were used as baseline and recorded weekly after each injections till 9 weeks then 4th and 12th week after completion of therapy.</p><p class="abstract"><strong>Results:</strong> 50 patients were the study population. The median age was 34.7 years with a female predominance. 23 patients were ASST positive and the rest were negative. Following treatment, ASST positive group had 69% improvement in TSS and ASST negative group had 61.5% improvement in TSS. There was statistically significant differences following treatment compared to baseline and between the two groups.</p><p><strong>Conclusions:</strong> AST as an adjunctive treatment for chronic urticaria shows promise for patients irrespective of ASST positivity and is more effective for ASST positive patients.</p>