L'Italo-Americano

THURSDAY, MAY 14, 2020 www.italoamericano.org 16 L'Italo-Americano C o V i D - 1 9 p a n - d e m i c a s o f 1 May 2020: (The Federal Guide- lines for stem- ming the spread of CoViD-19 [physical distancing and other public safety issues] expired as of midnight last night). G l o b a l l y - C o n f i r m e d C a s e s : 3 , 4 0 0 , 0 0 0 + ; Fatalities: 237,405+. Italia - Confirmed Cases: 207,000+; Fatalities: 28,236. U S - C o n f i r m e d C a s e s : 1 , 1 2 0 , 0 0 0 + ; F a t a l i t i e s : 64,876. C a l i f o r n i a - C o n f i r m e d Cases: 51,000+; Fatalities: 2,047. L o s A n g e l e s C o u n t y - Confirmed Cases: 23,200+; F a t a l i t i e s : 1 , 1 1 1 . V i l l a Scalabrini Confirmed Cases: 2 Residents, 2 Staff (publichealth.lacounty.gov ). To better grasp the difficul- ty in raising a vaccine and i n o b t a i n i n g v a l i d t e s t results, we must gain a bet- ter understating of how our immune system responds to S A R S - C o v 2 , t h e v i r u s responsible for CoViD-19. I n b r i e f , w h e n w e a r e exposed to a pathogen, be it a virus or a bacterium, certain white blood cells get engaged i n a p r o c e s s t h a t w e c a l l i m m u n e s u r v e i l l a n c e . Over the next 4-7 days, they get activated, they prolifer- ate, they produce factors that induce other "cousin" white blood cells to become activat- ed, proliferate, mature and establish memory: for bacte- ria, in the form of antibodies, for viruses, both of anti- bodies and of cytotoxic cells capable of killing the virally infected cells. The gen- eration of immunity as such varies among pathogens, but generally takes 10-14 days. That is why nucleic acid PCR tests detect the presence of the virus RNA right after infection, but serologic tests detect the presence of anti- bodies against the virus only, a n d a t b e s t , o n e - t o - t w o weeks after infection. How l o n g d o t h e s e a n t i b o d i e s remain detectable varies widely across pathogens. W e d o n o t k n o w f o r h o w many days, weeks or months a c t i v e i m m u n i t y a g a i n s t SARS-Cov2 remains in our system, in part because the virus has mutated close to 35 t i m e s s i n c e i t w a s f i r s t reported in late December 2019. T h e s e i m m u n o l o g i c a l events occur in lymph nodes and lymphoid organs distrib- uted throughout the body (systemic immunity). They c a n a l s o o c c u r i n l y m p h nodes that are found in the mucus membranes of the nose, mouth, bronchi, lungs, and gastrointestinal tract (mucosal immunity). When a pathogen triggers systemic immunity, B cells, a population of white blood c e l l s t h a t a r e s o c a l l e d because, in birds, they devel- op in the Bursa of Fabricius, proliferate and produce spe- cific antibodies against the pathogen. The first antibody is immunologulin M (IgM), whose levels in blood rise fast, but last only a few days. D u r i n g t h a t t i m e B c e l l s mature, proliferate and pro- duce IgG: highly specific and potent antibodies against the pathogen, whose blood levels are elevated and sustained for some pathogens up to many years or decades. In other words, exposure to a given pathogen triggers sys- temic immunity to produce IgG that provides long-term specific protection against that pathogen. That is the simple prin- ciple behind vaccines. The caveat is that each pathogen is unique for the specificity of the IgM and IgG it engenders, and for the sta- bility of this antibody protec- tion over time. Early studies suggest that "the immunity generated by SARS-Cov2 may be short- lived," meaning that the IgG species produced in response to the virus responsible for CoViD-19 may be stable only for a relatively short length of time. If these data are con- firmed, it will throw a signifi- cant wrench in our efforts to produce a vaccine. (Note: I have great respect for Dr. Fauci and trust that his "hope"we will have mil- lions of doses of effective vac- c i n e a g a i n s t S A R S - C o v 2 "within eight months" is well founded …but hope is not a plan, and reality may dictate other less propitious scenar- ios). W h e n w e h e a r t h a t t h e plasma of recovered CoViD- 19 patients holds promise for therapeutic use, here again, we must apply caution: if, in fact the IgG against SARS- Cov2 is short-lived, then we have only a tight window of time during which these anti- bodies might be protective to other patients. It is timely and critical that researchers establish the timeframe with- in which IgG from recovered patients can effectively be a d m i n i s t e r e d t o a c t i v e patients. That timeline will i n f o r m t h e f e a s i b i l i t y o f viable vaccines. But – there is always a "but" in the biological sci- e n c e s – t h e i m m u n e response against SARS-Cov2 i s p o s s i b l y — p r o b a b l y — greater in mucosal tissues than systemically, simply because the virus infects via the mucosa of the mouth, n o s e a n d e y e s . M u c o s a l Per Saperne Di Più: CoViD-19, a word with Francesco Chiappelli Issue 4, Dott. Francesco Chiappelli, Prof. Emerito UCLA Center for the Health Sciences immunity is also driven by a n t i b o d i e s , b u t g e n e r a l l y does not result in IgG, but mainly in IgA, which can be found in two forms: blood serum IgA involved in anti- body-mediated cytotoxicity, and secretory IgA in mucosal surfaces. IgA also exists in two classes, which determine their specific function and binding properties: IgA 1 in serum, IgA 2 at mucosal sites. We have close to no clinical research data at this point about IgA response to SARS- Cov2; and most – most, not a l l - s e r o l o g i c t e s t i n g f o r C o V i D - 1 9 i s d o n e n o t o n mucosal, but on blood serum samples for IgM and IgG, but not IgA. In short, we are far from having the necessary basic data for confidently having a vaccine. We are still far, in fact, from really understand- ing how immunity is mount- ed against this virus and its multiple mutants. The second aspect of sys- temic and mucosal immunity consists of two major sets of e v e n t s , w h i c h o v e r l a p t o some extent, cross-feed and mutually regulate. In brief, there is a cellular component, cell-mediated immunity, and there is the soluble immunity component mediated by the soluble factors it generates. The B cells mentioned above b e l o n g t o c e l l - m e d i a t e d immunity, and the Ig they produce are part of soluble i m m u n i t y . O t h e r c o m p o - nents of the former are T cells, natural killer cells, and a n t i g e n - p r e s e n t i n g c e l l s . Other components of the lat- ter are the large family of cytokines, factors that medi- ate, modulate and regulate immune cells proliferation and maturation. W h e n u n r e g u l a t e d , cytokines are released as a tsunami, the cytokine storm, which can generate patholo- gies in and of itself, destroy- i n g c e l l s a n d t i s s u e s . Regulatory T cells secrete interleukin(IL)-10, a power- fully inhibitory cytokine that prevents or attenuates the cytokine storm. Stress, gender hormones, (mal)nutrition, lack of sleep, Continued to page 18 NEWS & FEATURES TOP STORIES PEOPLE EVENTS

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