Coronavirus disease‐2019 (COVID‐19) was declared a global pandemic on 11 March 2020. Scientists and clinicians must acknowledge that severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has the potential to attack the human body in multiple ways simultaneously and exploit any weaknesses of its host. A multipronged attack could potentially explain the severity and extensive variety of signs and symptoms observed in patients with COVID‐19. Understanding the diverse tactics of this virus to infect the human body is both critical and incredibly complex. Although patients diagnosed with COVID‐19 have primarily presented with pulmonary involvement, viral invasion, and injury to diverse end organs is also prevalent and well documented in these patients, but has been largely unheeded. Human organs known for angiotensin‐converting enzyme 2 (ACE2) expression including the gastrointestinal tract, kidneys, heart, adrenals, brain, and testicles are examples of extra pulmonary tissues with confirmed invasion by SARS‐CoV‐2. Initial multiple organ involvement may present with vague signs and symptoms to alert health care professionals early in the course of COVID‐19. Another example of an ongoing, yet neglected element of the syndromic features of COVID‐19, are the reported findings of loss of smell, altered taste, ataxia, headache, dizziness, and loss of consciousness, which suggest a potential for neural involvement. In this review, we further deliberate on the neuroinvasive potential of SARS‐CoV‐2, the neurologic symptomology observed in COVID‐19, the host‐virus interaction, possible routes of SARS‐CoV‐2 to invade the central nervous system, other neurologic considerations for patients with COVID‐19, and a collective call to action.

In early 2020, a global emergency was upon us in the form of the coronavirus disease 2019 (COVID-19) pandemic. While horrific in its health, social and economic devastation, one silver lining to this crisis has been a rapid mobilization of cross-institute, and even cross-country teams that shared common goals of learning as much as we could as quickly as possible about the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and how the immune system would respond to both the virus and COVID-19 vaccines. Many of these teams were formed by women who quickly realized that the classical model of "publish first at all costs" was maladaptive for the circumstances and needed to be supplanted by a more collaborative solution-focused approach. This review is an example of a collaboration that unfolded in separate countries, first Canada and the United States, and then also Israel. Not only did the collaboration allow us to cross-validate our results using different hands/techniques/ samples, but it also took advantage of different vaccine types and schedules that were rolled out in our respective home countries. The result of this collaboration was a new understanding of how mucosal immunity to SARS-CoV-2 infection vs COVID-19 vaccination can be measured using saliva as a biofluid, what types of vaccines are best able to induce (limited) mucosal immunity, and what are potential correlates of protection against breakthrough infection. In this review, we will share what we have learned about the mucosal immune response to SARS-CoV-2 and to COVID-19 vaccines and provide a perspective on what may be required for next-generation pansarbecoronavirus vaccine approaches.

Vaccination induced antibody and T-cell immune responses are important for systemic protection from COVID-19. Because SARS-CoV-2 infects and is transmitted by oral-pharyngeal mucosa, we wished to test mucosal antibodies elicited by natural infection or intramuscular vaccine injection. In a non-randomized observational study, we measured antibodies against the SARS-CoV-2 RBD in plasma and saliva from convalescent or vaccinated individuals and tested their neutralizing potential using a replication competent rVSV-eGFP-SARS-CoV-2. We found IgG and IgA anti-RBD antibodies as well as neutralizing activity in convalescent plasma and saliva. Two doses of mRNA vaccination (BNT162b2 or mRNA-1273) induced high levels of IgG anti-RBD in saliva, a subset of whom also had IgA, and significant neutralizing activity. We detected anti-RBD IgG and IgA with significant neutralizing potential in the plasma of single dose Ad26.COV2.S vaccinated individuals, and we detected slight amounts of anti-RBD antibodies in matched saliva. The role of salivary antibodies in protection against SARS-CoV-2 infection is unknown and merits further investigation. This study was not designed to, nor did it study the full kinetics of the antibody response or protection from infection, nor did it address variants of SARS-CoV-2.

The 2019 novel coronavirus disease (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a zoonotic disease that is dominated by pulmonary symptoms. However, recent reports of isolation of the virus from cerebrospinal fluid (CSF) coupled with radiological evidence of zones of necrosis in the brain, have elucidated the neurotropic potential of SARS-CoV-2. The acute respiratory failure seen in patients with COVID-19 is alarming and could be due to the effects of SARS-CoV-2 on the central respiratory regulatory centers in the brainstem. Appropriate interventions can be implemented to prevent severe outcomes of neurological invasion by SARS-CoV-2 to reduce the morbidity and mortality of patients with COVID-19. It is of paramount importance that the scientific community alerts the healthcare professionals of the pieces of evidence that can herald them on the covert neurological deficits in progress in COVID-19.

Borrelia burgdorferi is a bacterial spirochete that can cause Lyme disease (LD) after infecting a susceptible host. Immune responses to the bacteria are highly variable and host specific. The murine substrain, C3H/HeJ, is a frequently utilized model for LD. Interestingly, we observed dermatitis with flaky lesions of the tail skin on C3H/HeJ after a year of infection with B. burgdorferi. Female C3H/HeJ mice aged 6-8 weeks, 1 year, or 2 years were infected intraperitoneally with 105 B. burgdorferi spirochetes. Mouse tails were evaluated by gross examination and histology either 2 months or 24 months post-infection. Dermatitis worsened over the course of untreated infection, with ulceration, hemorrhaging, flaking, hair loss, and dark lesions as well as spongiosis and acanthosis. These features of atopic dermatitis were present in infected mice after 1 year of age. This relationship among LD, atopic dermatitis, and host age seen in the C3H/HeJ mouse model is consistent with a large pool of human epidemiological data (342,499 individuals) from Finland. We identified 5,248 individuals with LD and 17,233 with atopic dermatitis in the FinnGen biobank. Retrospective analysis shows LD is associated with atopic dermatitis (OR = 1.91 [1.68 -2.37], P < 2e-16). Repeat visits for LD complications (3 or more visits versus 1 visit) were associated with atopic dermatitis (OR = 2.19 [1.35-3.55], P = 0.0014) and risk of developing atopic dermatitis over time (HR=2.26 [1.54-3.95] , P = 0.0017). Data from mice and humans reveal a novel relationship among LD, age, and atopic dermatitis. Through defined pathological scoring, we demonstrate that the onset of murine Lyme disease-associated atopic dermatitis is exacerbated by increased host age at time of B. burgdorferi infection. In humans, a diagnosis of Lyme disease in the FinnGen registry was associated with atopic dermatitis and further research is warranted to establish causation.