SARS-CoV-2 Vaccine Induced Atypical Immune Responses in Antibody Defects: Everybody Does their Best

Background: Data on immune responses to SARS-CoV-2 in patients with Primary Antibody Deficiencies (PAD) are limited to infected patients and to heterogeneous cohorts after immunization. Methods: Forty-one patients with Common Variable Immune Deficiencies (CVID), six patients with X-linked Agammaglobulinemia (XLA), and 28 healthy age-matched controls (HD) were analyzed for anti-Spike and anti-receptor binding domain (RBD) antibody production, generation of Spike-specific memory B-cells, and Spike-specific T-cells before vaccination and one week after the second dose of BNT162b2 vaccine. Results: The vaccine induced Spike-specific IgG and IgA antibody responses in all HD and in 20% of SARS-CoV-2 naive CVID patients. Anti-Spike IgG were detectable before vaccination in 4 out 7 CVID previously infected with SARS-CoV-2 and were boosted in six out of seven patients by the subsequent immunization raising higher levels than patients naïve to infection. While HD generated Spike-specific memory B-cells, and RBD-specific B-cells, CVID generated Spike-specific atypical B-cells, while RBD-specific B-cells were undetectable in all patients, indicating the incapability to generate this new specificity. Specific T-cell responses were evident in all HD and defective in 30% of CVID. All but one patient with XLA responded by specific T-cell only. Conclusion: In PAD patients, early atypical immune responses after BNT162b2 immunization occurred, possibly by extra-follicular or incomplete germinal center reactions. If these responses to vaccination might result in a partial protection from infection or reinfection is now unknown. Our data suggests that SARS-CoV-2 infection more effectively primes the immune response than the immunization alone, possibly suggesting the need for a third vaccine dose for patients not previously infected

Clinical management of patients with primary immunodeficiencies during the COVID-19 pandemic

Introduction: Patients affected by Inborn Errors of Immunity (IEI) represent a potential group-at-risk in the current COVID-19 pandemic. Studies on large and small cohorts of IEI reported a huge variability clinical manifestations associated to SARS-Cov-2, ranging from asymptomatic, mild, moderate/severe to death. A great impulse to improve remote assistance programs and to switch to home-based treatment to reduce mobility and face to face contacts has been implemented. Areas covered: The authors completed a comprehensive review of the literature by searching the PubMed database for studies on large and small cohorts and case reports of IEI patients with COVID-19, with the aim to provide useful information for their clinical management during the COVID-19 pandemic. Expert opinion: Surprisingly, a low number of IEI patients affected by SARS-Cov-2 were reported with a risk to die for COVID-19 overlapping that of the general population. The low number might be explained by the choice of most physicians to inform early in the pandemic about safety measures, to switch most of the IEI patients to home therapy and to remote assistance. The guidelines issued by the scientific societies and periodically updated, represent the best tool for the clinical management of IEI patients

Mechanistic understanding of innate and adaptive immune responses in SARS-CoV-2 infection

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have triggered global pandemic that continue to impact adversely human health. New understanding has emerged about the innate and adaptive immune responses elicited in SARS-CoV-2 infection. The understanding of innate immune responses generated in hosts early in SARS-CoV-2 infection is vital for treatment efforts. Antiviral cytokines are released by innate immune cells in response to viral infections that play a pivotal role in limiting viral replication, pathology and generating optimal adaptive immune responses alongside the long-term memory responses against reinfections. One aspect of innate immune response generated against SARS-CoV-2 in vivo and which has received much attention has been high proinflammatory cytokine release in COVID-19 patients. Another vital discovery has been that the antiviral cytokine type I Interferon (IFN) family IFN-α mediates upregulation of angiotensin converting enzyme 2 (ACE2) membrane protein in airway epithelial cells. ACE2 is a receptor that SARS-CoV-2 binds to infect host cells. New understanding has emerged about the mechanism of SARS-CoV-2 induced exaggerated proinflammatory cytokine release as well as transcriptional regulation of ACE2. This review discusses various mechanisms underlying SARS-CoV-2 induced exaggerated proinflammatory cytokine response as well as transcriptional regulation of ACE2 receptor. We further elaborate on adaptive and memory responses generated against SARS-CoV-2

Humans with inherited MyD88 and IRAK-4 deficiencies are predisposed to hypoxemic COVID-19 pneumonia

X-linked recessive deficiency of TLR7, a MyD88- and IRAK-4–dependent endosomal ssRNA sensor, impairs SARS-CoV-2 recognition and type I IFN production in plasmacytoid dendritic cells (pDCs), thereby underlying hypoxemic COVID-19 pneumonia with high penetrance. We report 22 unvaccinated patients with autosomal recessive MyD88 or IRAK-4 deficiency infected with SARS-CoV-2 (mean age: 10.9 yr; 2 mo to 24 yr), originating from 17 kindreds from eight countries on three continents. 16 patients were hospitalized: six with moderate, four with severe, and six with critical pneumonia, one of whom died. The risk of hypoxemic pneumonia increased with age. The risk of invasive mechanical ventilation was also much greater than in age-matched controls from the general population (OR: 74.7, 95% CI: 26.8–207.8, P < 0.001). The patients’ susceptibility to SARS-CoV-2 can be attributed to impaired TLR7-dependent type I IFN production by pDCs, which do not sense SARS-CoV-2 correctly. Patients with inherited MyD88 or IRAK-4 deficiency were long thought to be selectively vulnerable to pyogenic bacteria, but also have a high risk of hypoxemic COVID-19 pneumonia

IMPORTANCE OF NUTRIENTS IN COMBATING WITH COVID-19

In present scenario COVID-19 pandemic is the leading challenge across the globe. This new coronavirus disease is declared to be a global pandemic by the World Health Organization. At present, we are dependent upon lifesaving drugs/vaccines. In addition to the drugs, the essential advisories are to be followed to prevent the spread of COVID-19 like maintaining personal hygiene, physical distancing, respiratory hygiene, vaccination, healthy and balanced nutrition and strong immune system. Our immune system protects against diseases and maintains health. Good healthy nutrition increases the immunity and controls the diseases. We need to pay attention to the importance of nutrition in curing the covid 19. This can help us to understand the relation between disease and our dietary intake. A number of vitamins (A, B6, B12, folate, C, D and E) and trace elements (zinc, copper, selenium, iron) help in maintaining the human immune system and prevent the infections. Vitamin A controls dendritic cell and CD4+ T lymphocyte maturation. Vitamins B6, B12 and folate are useful for proper functioning of natural killer cells and CD8+ cytotoxic T lymphocytes. Vitamin C fights against infection and helps in phagocytosis and bacterial killing, natural killer cell activity, T lymphocyte function and antibody production. Vitamin D improves cellular immunity. Vitamin E helps in cell-mediated immune responses. Trace amount of zinc increases the proliferation of CD8+ cytotoxic T lymphocytes and provides antiviral defence. Trace elements like copper has antiviral properties. Iron is also important for maintaining the immunity. In additions to these nutrients gut micro bacterias are found to be protective against respiratory infection. In this article the role of specific nutrients in the immune system, with regard to antiviral defences have been summarised

Mechanistic Insight into the role of Vitamin D and Zinc in Modulating Immunity Against COVID-19: A View from an Immunological Standpoint

The pathophysiology of coronavirus disease-19 (COVID-19) is characterized by worsened inflammation because of weakened immunity, causing the infiltration of immune cells, followed by necrosis. Consequently, these pathophysiological changes may lead to a life-threatening decline in perfusion due to hyperplasia of the lungs, instigating severe pneumonia, and causing fatalities. Additionally, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause mortality due to viral septic shock, resulting from unrestrained and backfiring immune reactions to the pathogen. Sepsis can cause premature organ failure in COVID-19 patients, as well. Notably, vitamin D and its derivatives and minerals, such as zinc and magnesium, have been reported to improve the immune system against respiratory illnesses. This comprehensive review aims to provide updated mechanistic details of vitamin D and zinc as immunomodulators. Additionally, this review also focuses on their role in respiratory illnesses, while specifically delineating the plausibility of employing them as a preventive and therapeutic agent against current and future pandemics from an immunological perspective. Furthermore, this comprehensive review will attract the attention of health professionals, nutritionists, pharmaceuticals, and scientific communities, as it encourages the use of such micronutrients for therapeutic purposes, as well as promoting their health benefits for a healthy lifestyle and wellbeing

A NUTRITION VIEW OF COVID 19 IN THE PANDEMIC

COVID-19 is a disease caused by a coronavirus, called SARS-CoV-2. This virus has become a major public health concern worldwide, causing a collective outbreak, leading to the pandemic in 2020. People become infected with other common coronaviruses throughout their lives, but currently the concern is the COVID-19 type due to its severity in some cases. The immune system protects the body against external aggressions and preserves the body\u27s homeostasis, and nutrients are involved in the development and preservation of this system. Considering the degree of complications that can occur in an individual with COVID-19, regardless of their age group, and in some cases even lethal, there was an interest in researching studies about this disease, and which nutrients are mentioned in the literature regarding immunity in this disease. The aims of this research were to describe concepts about the disease COVID-19 and to identify nutrients involved in the immunity and treatment of this disease, through a literature review in the period from December 2019 to October 2020. There is no doubt that it is essential to maintain an adequate nutritional status, through a balanced diet that can contribute to a better coping with the infectious state. Supplementation of vitamins, minerals, probiotics and prebiotics can provide the immune system, several of them were cited as an adjunct to the treatment of COVID-19, including their doses, but there was a lack of agreement regarding the dose of nutrients. Obviously maintaining social distance, wearing masks and proper hygiene are essential to reduce the risk of contamination, while not having access to vaccination

COVID-19 and Nutrition

Many individuals who contract COVID-19 and experience poor outcomes are also found to be deficient in certain vitamins and minerals. As a result, many nutrients have been related to improved outcomes for patients suffering from COVID-19. While it is not proven that increased intake of any one vitamin or mineral can prevent COVID-19, the supplementation of specific vitamins or minerals such as vitamin C, vitamin D, zinc, and magnesium could impact the risk of getting COVID-19 and the severity of cases of COVID-19. Positive benefits are expected from this relationship because certain vitamins and minerals have been known to support the immune system and impact the effects of respiratory diseases. Since COVID-19 impacts populations differently, nutritional measures of prevention and treatment may be more beneficial for those who are more at risk of developing COVID-19 and experiencing poorer outcomes