Applying Immune Instincts and Maternal Intelligence from Comparative Microbiology to COVID-19.

New data specific to COVID-19 are emerging quickly on key issues of immunity and prevention, but past research in coronavirology and for other human pathogens (e.g., Mycoplasma pneumoniae) has been available and of great relevance. Considerable study of endemic human coronaviruses has shown that neutralizing antibody correlates with protection, but effective clinical protection is variable for subsequent virus exposure. Animal coronavirus research has emphasized the importance of local mucosal protection (especially IgA) and systemic responses. Animal model and human post-infection studies for SARS-CoV and MERS-CoV are largely corroborative. Whether for passive therapeutic strategies or vaccination, these findings provide a template for COVID-19. Many approaches to vaccination have emerged, and there may be more than one vaccine that will be applied, but individualized obstacles and concerns for administration, efficacy, and safety are inevitable. Regardless of safeguards or promises that may be understood from laboratory or vertebrate experiments, observations from large-scale human trials will ultimately prove to shape the medical future. Focus on common mucosal immunity can be underrated, and equally or more, focus on lactogenic immunity may be underestimated. In understanding both passive immunity and protection, the body is already primed to educate us with decisions of what constitutes protection and harm. This review provides key insights that drive hypotheses into how the instinct of immunity and the intelligence of the maternal component of the common mucosal immune system has already guided us and may continue to do so effectively into a bright and safe future.

Disinfection and decontamination in the context of SARS-CoV-2-specific data.

Given the high transmissibility of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as witnessed early in the coronavirus disease 2019 (COVID-19) pandemic, concerns arose with the existing methods for virus disinfection and decontamination. The need for SARS-CoV-2-specific data stimulated considerable research in this regard. Overall, SARS-CoV-2 is practically and equally susceptible to approaches for disinfection and decontamination that have been previously found for other human or animal coronaviruses. The latter have included techniques utilizing temperature modulation, pH extremes, irradiation, and chemical treatments. These physicochemical methods are a necessary adjunct to other prevention strategies, given the environmental and patient surface ubiquity of the virus. Classic studies of disinfection have also allowed for extrapolation to the eradication of the virus on human mucosal surfaces by some chemical means. Despite considerable laboratory study, practical field assessments are generally lacking and need to be encouraged to confirm the correlation of interventions with viral eradication and infection prevention. Transparency in the constitution and use of any method or chemical is also essential to furthering practical applications.

Passive Immunity Should and Will Work for COVID-19 for Some Patients.

In the absence of effective antiviral chemotherapy and still in the context of emerging vaccines for severe acute respiratory syndrome-CoV-2 infections, passive immunotherapy remains a key treatment and possible prevention strategy. What might initially be conceived as a simplified donor-recipient process, the intricacies of donor plasma, IV immunoglobulins, and monoclonal antibody modality applications are becoming more apparent. Key targets of such treatment have largely focused on virus neutralization and the specific viral components of the attachment Spike protein and its constituents (e.g., receptor binding domain, N-terminal domain). The cumulative laboratory and clinical experience suggests that beneficial protective and treatment outcomes are possible. Both a dose- and a time-dependency emerge. Lesser understood are the concepts of bioavailability and distribution. Apart from direct antigen binding from protective immunoglobulins, antibody effector functions have potential roles in outcome. In attempting to mimic the natural but variable response to infection or vaccination, a strong functional polyclonal approach attracts the potential benefits of attacking antigen diversity, high antibody avidity, antibody persistence, and protection against escape viral mutation. The availability and ease of administration for any passive immunotherapy product must be considered in the current climate of need. There is never a perfect product, but yet there is considerable room for improving patient outcomes. Given the variability of human genetics, immunity, and disease, and given the nuances of the virus and its potential for change, passive immunotherapy can be developed that will be effective for some but not all patients. An understanding of such patient variability and limitations is just as important as the understanding of the direct interactions between immunotherapy and virus.

Untangling the Intricacies of Infection, Thrombosis, Vaccination, and Antiphospholipid Antibodies for COVID-19.

Advanced SARS-CoV-2 infections not uncommonly associate with the occurrence of silent or manifest thrombotic events which may be found as focal or systemic disease. Given the potential complexity of COVID-19 illnesses, a multifactorial causation is likely, but several studies have focused on infection-induced coagulopathy. Procoagulant states are commonly found in association with the finding of antiphospholipid antibodies. The correlation of the latter with thrombosis and/or clinical severity remains controversial. Although measures of antiphospholipid antibodies most commonly include assessments for lupus anticoagulant, anticardiolipin, and anti-ß2-glycoprotein-I antibodies, lesser common antibodies have been detected, and there remains speculation that other yet undiscovered autoimmune thrombotic events may yet be found. The recent discovery of post-vaccination thromboses associated with platelet factor 4 antibody has created another level of concern. The pathogenesis of antiphospholipid antibodies and their role in COVID-19-related thrombosis deserves further attention. The multifactorial nature of thrombosis associated with both infection and vaccination should continue to be studied as new events unfold. Even if a cause-and-effect relationship is variable at best, such dedicated research is likely to generate other valuable insights that are applicable to medicine generally.

The Complexity of Co-Infections in the Era of COVID-19.

The current frequency of COVID-19 in a pandemic era ensures that co-infections with a variety of co-pathogens will occur. Generally, there is a low rate of bonafide co-infections in early COVID-19 pulmonary infection as currently appreciated. Reports of high co-infection rates must be tempered by limitations in current diagnostic methods since amplification technologies do not necessarily confirm live pathogen and may be subject to considerable laboratory variation. Some laboratory methods may not exclude commensal microbes. Concurrent serodiagnoses have long been of concern for accuracy in these contexts. Presumed virus co-infections are not specific to COVID-19. The association of influenza viruses and SARS-CoV-2 in co-infection has been considerably variable during influenza season. Other respiratory virus co-infections have generally occurred in less than 10% of COVID-19 patients. Early COVID-19 disease is more commonly associated with bacterial co-pathogens that typically represent usual respiratory micro-organisms. Late infections, especially among severe clinical presentations, are more likely to be associated with nosocomial or opportunistic pathogens given the influence of treatments that can include antibiotics, antivirals, immunomodulating agents, blood products, immunotherapy, steroids, and invasive procedures. As anticipated, hospital care carries risk for multi-resistant bacteria. Overall, co-pathogen identification is linked with longer hospital stay, greater patient complexity, and adverse outcomes. As for other viral infections, a general reduction in the use of empiric antibiotic treatment is warranted. Further insight into co-infections with COVID-19 will contribute overall to effective antimicrobial therapies and disease control.

In pursuit of the right tail for the COVID-19 incubation period.

Definition of the incubation period for COVID-19 is critical for implementing quarantine and thus infection control. Whereas the classical definition relies on the time from exposure to time of first symptoms, a more practical working definition is the time from exposure to time of first live virus excretion. For COVID-19, average incubation period times commonly span 5-7 days which are generally longer than for most typical other respiratory viruses. There is considerable variability reported however for the late right-hand statistical distribution. A small but yet epidemiologically important subset of patients may have the late end of the incubation period extend beyond the 14 days that is frequently assumed. Conservative assumptions of the right tail end distribution favor safety, but pragmatic working modifications may be required to accommodate high rates of infection and/or healthcare worker exposures. Despite the advent of effective vaccines, further attention and study in these regards are warranted. It is predictable that vaccine application will be associated with continued confusion over protection and its longevity. Measures for the application of infectivity will continue to be extremely relevant.

A Comprehensive Analysis of Maternal and Newborn Disease and Related Control for COVID-19.

The maternal-fetal/newborn unit is established at risk for COVID-19 infection. This narrative review summarizes the contemporary and cumulative publications which detail maternal infection, antenatal and newborn infections, and maternal/fetal/newborn management and prevention. There is a wide spectrum of maternal disease, but the potential for severe disease albeit in a minority is confirmed. COVID-19 carries risk for preterm delivery. Pregnant females can suffer multisystem disease, and co-morbidities play a significant role in risk. Congenital infection has been supported by several anecdotal reports, but strong confirmatory data are few. No typical congenital dysmorphisms are evident. Nevertheless, placental vascular compromise must be considered a risk for the fetus during advanced maternal infections. Clinical manifestations of newborn infection have been mild to moderate and relatively uncommon. Proven antiviral therapy is of yet lacking. The mode of delivery is a medical decision that must include patient risk assessment and patient directives. Both presymptomatic and asymptomatic mothers and offspring can complicate infection control management with the potential for spread to others in several regards. In the interim, infections of the maternal-fetal-newborn unit must be taken seriously both for the disease so caused and the potential for further dissemination of disease.

Features of enteric disease from human coronaviruses: Implications for COVID-19.

Coronaviruses have long been studied in both human and veterinary fields. Whereas the initial detection of endemic human respiratory coronaviruses was problematic, detection of these and newly discovered human coronaviruses has been greatly facilitated with major advances in the laboratory. Nevertheless, technological factors can affect the accuracy and timeliness of virus detection. Many human coronaviruses can be variably found in stool samples. All human coronaviruses have been variably associated with symptoms of gastroenteritis. Coronaviruses can occasionally be cultured from enteric specimens, but most detection is accomplished with genetic amplification technologies. Excretion of viral RNA in stool can extend for a prolonged period. Culture-positive stool samples have been found to exceed a fourteen day period after onset of infection for some coronaviruses. Virus can also sometimes be cultured from patients' respiratory samples during the late incubation period. Relatively asymptomatic patients may excrete virus. Both viable and nonviable virus can be found in the immediate environment of the patient, the health care worker, and less often the public. These lessons from the past study of animal and human coronaviruses can be extended to presumptions for severe acute respiratory syndrome coronavirus 2. Already, the early reports from the coronavirus disease-2019 pandemic are confirming some concerns. These data have the cumulative potential to cause us to rethink some current and common public health and infection control strategies.