COVID-19 severity affected by proportion of antibodies targeting crucial viral protein -- ScienceDaily
COVID-19 severity affected by proportion of antibodies targeting crucial viral protein
COVID-19 antibodies preferentially target a different part of the virus in mild cases of COVID-19 than they do in severe cases, and wane significantly within several months of infection, according to a new study by researchers at Stanford Medicine.
The findings identify new links between the course of the disease and a patient's immune response. They also raise concerns about whether people can be re-infected, whether antibody tests to detect prior infection may underestimate the breadth of the pandemic and whether vaccinations may need to be repeated at regular intervals to maintain a protective immune response.
"This is one of the most comprehensive studies to date of the antibody immune response to SARS-CoV-2 in people across the entire spectrum of disease severity, from asymptomatic to fatal," said Scott Boyd, MD, PhD, associate professor of pathology. "We assessed multiple time points and sample types, and also analyzed levels of viral RNA in patient nasopharyngeal swabs and blood samples. It's one of the first big-picture looks at this illness."
The study found that people with severe COVID-19 have low proportions of antibodies targeting the spike protein used by the virus to enter human cells compared with the number of antibodies targeting proteins of the virus's inner shell.
Boyd is a senior author of the study, which was published Dec. 7 in Science Immunology. Other senior authors are Benjamin Pinsky, MD, PhD, associate professor of pathology, and Peter Kim, PhD, the Virginia and D. K. Ludwig Professor of Biochemistry. The lead authors are research scientist Katharina Röltgen, PhD; postdoctoral scholars Abigail Powell, PhD, and Oliver Wirz, PhD; and clinical instructor Bryan Stevens, MD.
The researchers studied 254 people with asymptomatic, mild or severe COVID-19 who were identified either through routine testing or occupational health screening at Stanford Health Care or who came to a Stanford Health Care clinic with symptoms of COVID-19. Of the people with symptoms, 25 were treated as outpatients, 42 were hospitalized outside the intensive care unit and 37 were treated in the intensive care unit. Twenty-five people in the study died of the disease.
SARS-CoV-2 binds to human cells via a structure on its surface called the spike protein. This protein binds to a receptor on human cells called ACE2. The binding allows the virus to enter and infect the cell. Once inside, the virus sheds its outer coat to reveal an inner shell encasing its genetic material. Soon, the virus co-opts the cell's protein-making machinery to churn out more viral particles, which are then released to infect other cells.
Antibodies that recognize and bind to the spike protein block its ability to bind to ACE2, preventing the virus from infecting the cells, whereas antibodies that recognize other viral components are unlikely to prevent viral spread. Current vaccine candidates use portions of the spike protein to stimulate an immune response.
Boyd and his colleagues analyzed the levels of three types of antibodies -- IgG, IgM and IgA -- and the proportions that targeted the viral spike protein or the virus's inner shell as the disease progressed and patients either recovered or grew sicker. They also measured the levels of viral genetic material in nasopharyngeal samples and blood from the patients. Finally, they assessed the effectiveness of the antibodies in preventing the spike protein from binding to ACE2 in a laboratory dish.
"Although previous studies have assessed the overall antibody response to infection, we compared the viral proteins targeted by these antibodies," Boyd said. "We found that the severity of the illness correlates with the ratio of antibodies recognizing domains of the spike protein compared with other nonprotective viral targets. Those people with mild illness tended to have a higher proportion of anti-spike antibodies, and those who died from their disease had more antibodies that recognized other parts of the virus."
As in other studies, the researchers found that people with asymptomatic and mild illness had lower levels of antibodies overall than did those with severe disease. After recovery, the levels of IgM and IgA decreased steadily to low or undetectable levels in most patients over a period of about one to four months after symptom onset or estimated infection date, and IgG levels dropped significantly.
"This is quite consistent with what has been seen with other coronaviruses that regularly circulate in our communities to cause the common cold," Boyd said. "It's not uncommon for someone to get re-infected within a year or sometimes sooner. It remains to be seen whether the immune response to SARS-CoV-2 vaccination is stronger, or persists longer, than that caused by natural infection. It's quite possible it could be better. But there are a lot of questions that still need to be answered."
"For example, if someone has already been infected, should they get the vaccine? If so, how should they be prioritized?" Boyd said. "How can we adapt seroprevalence studies in vaccinated populations? How will immunity from vaccination differ from that caused by natural infection? And how long might a vaccine be protective? These are all very interesting, important questions."
Rest of story at link
https://www.reddit.c...ne_ingredients/Shows the spike protein is in the vaccines (it doesn't mention surface protein).
Is there a difference, naturally, in how the immune system builds immunity for one versus the other?
For example, is Thymic immunity responsible for the spike protein immunity, but another part like marrow responsible for surface, deeper, response?
Nebulised interferon beta-1a for patients with COVID-19
https://www.thelance...IIS2213-2600(20)30523-3/fulltext
"In The Lancet Respiratory Medicine, Phillip Monk and colleagues1 report the results of a randomised, double-blind, placebo-controlled phase 2 pilot trial of nebulised interferon beta-1a in 101 adults admitted to hospital with COVID-19. The authors found that patients who received nebulised interferon beta-1a had significantly greater odds of clinical improvement across the WHO Ordinal Scale for Clinical Improvement than those who received placebo, both on day 15/16 (odds ratio [OR] 2·32 [95% CI 1·07–5·04]; p=0·033) and on day 28 (3·15 [1·39–7·14]; p=0·006). However, there was no significant difference between treatment groups in the odds of hospital discharge by day 28: 39 (81%) of 48 patients had been discharged in the nebulised interferon beta-1a group compared with 36 (75%) of 48 in the placebo group (OR 1·84 [95% CI 0·64–5·29]; p=0·26).
Type 1 interferons are among the first cytokines produced during a viral infection and promote both innate and adaptive immunity. Interferon beta has shown an antiviral effect against coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) in in-vitro studies and animal models.2 A recently published randomised clinical trial found that a combination of recombinant interferon beta-1b and lopinavir–ritonavir decreased mortality in patients with MERS-CoV infection.3 Clinical studies of SARS-CoV-2 found that a proportion of patients with severe COVID-19 had impaired type I interferon activity,4 potentially linked to autoantibodies against type I interferon.5 However, preliminary results from the SOLIDARITY/DisCoVeRy randomised clinical trial in more than 2000 patients showed no efficacy of subcutaneous interferon alone or with lopinavir–ritonavir.6 The results of the present pilot study,1 in contrast to the results of the SOLIDARITY trial, corroborate findings from in-vitro studies and animal models showing that the interferon pathway is crucial in controlling SARS-CoV-2 infection.
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How can we account for these apparently conflicting results? First, the population targeted by these studies was different. The population in the present pilot study1 was overall at a less severe stage of COVID-19 than that in the SOLIDARITY trial; no patients with invasive ventilation were included, whereas 8% of patients in SOLIDARITY were ventilated; and global mortality was 3% at 28 days in the present study versus 12% in SOLIDARITY. Second, the route of administration of interferon beta-1a was different in these studies: the present study used nebulised therapy that delivers interferon beta-1a directly to the respiratory tract, whereas the SOLIDARITY trial used subcutaneous interferon beta-1a. Nebulised therapy allows targeted delivery of interferon to the lungs, where it can induce the expression of interferon-stimulated genes that participate directly (eg, through degradation of viral RNA, interference with viral translation or assembly, and so on) or indirectly (via signalling and recruitment of monocytes or macrophages or T cells, increased antigen presentation and cross-presentation, and so on) in the antiviral response in the mucosa.7
The number of patients enrolled in the present study was small. Additionally, this study showed no impact of the evaluated treatment on time to discharge or on mortality, although the study was not adequately powered to analyse mortality outcomes. Larger randomised clinical trials are therefore needed to further investigate the effectiveness of nebulised interferon beta-1a therapy in this setting. The safety of nebulised interferon beta-1a will be of special interest since nebulisation of interferon has no marketing authorisation for any indication yet. Future trials should evaluate the effect of interferon beta-1a on inflammatory biomarkers and analyse virological data to better characterise the physiopathology underlying this drug. It will also be worthwhile to investigate whether interferon beta-1a has an impact on prolonged symptoms of COVID-19, especially pulmonary symptoms. Recent studies have found persistent dyspnoea in up to 40% of patients with COVID-19 at 2 months after disease onset8 and abnormalities in pulmonary function at 3 months. In light of the growing number of patients with SARS-CoV-2 infection, it is now crucial to find drugs that could prevent these pulmonary sequelae. Other issues that should be explored include the price and availability of interferon beta.
It is also important to define which population should be prioritised in subsequent large randomised clinical trials. To optimise the antiviral effect of interferon beta, there is a greater rationale to target patients at an early stage of the disease. Studies in mice with MERS-CoV infection have shown that the timing of type I interferon administration in coronavirus infections has a crucial role: antiviral effects were observed if type I interferon was administered shortly after infection, but type I interferon failed to inhibit viral replication and had side-effects when administered later.9 In patients with severe COVID-19, an exacerbated inflammatory response has been identified as a cause of pulmonary complications, and interferon beta-1a—a pro-inflammatory cytokine—could increase the inflammatory response and be associated with safety issues.10 Therefore, patients at an early stage of the disease, possibly in the outpatient setting, might be of interest for future randomised clinical trials of nebulised interferon beta-1a.
Despite the large number of clinical trials underway for the treatment of COVID-19, few antiviral drugs against SARS-CoV-2 have been identified. The findings of the present study are promising in this regard. They should be promptly evaluated in large randomised clinical trials, including academically led trials.
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In fact, I haven't even rated one of your posts negatively (or at all). 
