Research shows both coronavirus infection and vaccination offers immunity that can protect people from getting sick again. But by how much and for how long remains unclear — a scientific gap that only time could fill.
Regardless of how immunity is acquired, there’s no telling whose bodies will or won’t create effective antibodies, and why they last longer for some than others; doctors speculate age or certain medical conditions might play a role.
It also doesn’t help that the testing shortage that plagued the nation at the beginning of the pandemic will forever shield researchers from understanding the true impact of COVID-19.
The Centers for Disease Control and Prevention estimates that between February 2020 and March 2021, there were about 114.6 million total coronavirus infections in the U.S.. That’s about 81.1 million more cases than are confirmed as of June 17.
While people can gain immunity from both infection and vaccination, antibodies created from both routes target different parts of the virus, which leads to variations in the quality of protection.
It’s like a coin flip: risk contracting COVID-19 — and potentially becoming a long-hauler — or getting vaccinated. Some argue the final outcome is similar, but one is far more dangerous than the other.
Here’s what the latest data show about immunity from prior infection and vaccines.
Natural immunity from coronavirus infection
There are certain illnesses in which infection can offer more protection than a vaccine.
But if the novel coronavirus is anything like others in the coronavirus family, like the Middle East Respiratory Syndrome (MERS), then permanent protection after infection is unlikely.
Studies offer some positive clues, however.
Research published in February found that coronavirus patients gained “substantial immune memory” that involved all four major parts of the immune system: memory B cells, antibodies, memory CD4+ T cells and memory CD8+ T cells.
This protection lasted about six months after infection in most people, but for some, it remained for up to eight months, suggesting it could last even longer in some cases.
Separate research posted in April showed a history of COVID-19 among U.K. patients was associated with an 84% lower risk of reinfection for about seven months after testing positive.
Another non-peer reviewed study published in June found that over five months, 1,359 American health care workers who previously had COVID-19 and didn’t get vaccinated stayed clear of reinfection. The Cleveland Clinic researchers said, in the context of a short supply of vaccines globally, “a practical and useful message would be to consider symptomatic COVID-19 to be as good as having received a vaccine,” adding that people who’ve had the coronavirus “are unlikely to benefit from COVID-19 vaccination.”
While scientists cannot predict who will develop natural immunity, evidence shows people who had severe COVID-19 are more likely to develop a stronger immune response than those who had milder forms of the disease.
Immunity from COVID-19 vaccines
It’s also true that research shows COVID-19 vaccines offer protection against reinfection, although “breakthrough cases” can occur because no vaccine is 100% effective.
However, studies have found vaccine-derived antibodies are more robust compared to those from natural infection — and the job is done without causing illness or other long-term complications often brought on by the disease.
Two doctors from Italy compared the process of infection and vaccination in relation to variants to the plot of an action movie.
It “begins with a character (the virus) running freely across the globe, eluding capture until being finally sent to jail (built by natural immunity). However, if this prison is not secure enough, the virus could escape, aided by certain mutations,” Dr. Emanuele Andreano and Dr. Rino Rappuoli of the Monoclonal Antibody Discovery Lab, wrote in Nature. “Vaccine-induced immunity… should help ensure those escape routes are securely closed.”
An April study that has not been peer-reviewed found that two doses of either the Pfizer or Moderna vaccines offered 10 times higher levels of antibodies compared to those developed after natural infection.
Another April paper showed that people who were previously infected with the coronavirus experienced significant boosts in their preexisting antibodies after two doses of the Pfizer vaccine, which also offered protection against coronavirus variants.
“Vaccines actually, at least with regard to SARS-CoV-2, can do better than nature… They are better than the traditional response you get from natural infection,” White House chief medical adviser Dr. Anthony Fauci said during a COVID-19 briefing in May.
Exactly why vaccines appear to generate more robust immunity than natural infection remains unclear, but Dr. Sabra Klein, a virologist and professor of immunology at Johns Hopkins Bloomberg School of Public Health, said infection and vaccination work in different ways.
“The immune system of people who have been infected has been trained to target all these different parts of the virus called antigens. You’d think that would provide the strongest immunity, but it doesn’t,” Klein said. “The Pfizer or Moderna vaccines target just the spike protein — the part of the virus that is essential for invading cells.
“It’s like a big red button sitting on the surface of the virus. It’s really sticking out there, and it’s what our immune system sees most easily,” she continued. “By focusing on this one big antigen, it’s like you’re making our immune system put blinders on and only be able to see that one piece of the virus.”
In other words, vaccines work to strengthen immune responses gained during natural infection; that’s why health experts advise people who’ve had COVID-19 to still get vaccinated.
“There’s nothing deleterious about getting a boost to an immune response that you’ve had before,” Dr. Marion Pepper, an immunologist at the University of Washington in Seattle, told The New York Times. “You could get an actually even better immune response by boosting whatever immunity you had from the first infection by a vaccine.”
Follow more of our reporting on Full coverage of coronavirus in Washington
When you are looking for herbal immunity boosters, giloy and its supplements are quite popular in India. Giloy is not just used for reducing fever but is even a great choice for strengthening the immune system, keeping a check on blood pressure and sugar levels, improving metabolism, promoting healthy digestion and more. If you do not want to go for giloy juice, tablets or capsules, you can even take this immunity booster in the form of giloy powder.
Focus on your immune system and take the help of one of these packs of giloy powder that you can buy online. Have a look at this list of some of the most popular options that are worth your money and improve your overall health using natural products.
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If you are finding it hard to prepare kadha or other immunity booster drinks using giloy stem, you can take the help of this pack of stem powder. This organic powder is easy to add to the diet and can be used in multiple ways. Besides boosting immunity, it can help your body detox, reduce mental and physical stress and even reduce anxiety to an extent.
You can have this giloy powder with warm milk or water. The shelf life of this pack is 24 months from the date of manufacturing if you store it well.
In the market of healthcare supplements and products, Baidyanath has been a trusted name in India for years. This giloy powder by the brand is a great immunity booster and even helps in eliminating stomach disorders. So, your digestive system will stay healthy and the food that you take is digested properly.
You can take 1-2 spoons of this powder with lukewarm water as directed by your physician to see a visible difference in your overall health in a few days. Regular consumption of this powder can even keep minor seasonal infections away.
This pack of giloy powder can be another good option to consider buying online for your overall health and immunity. This powder is sourced from forests and is organic. So, you need not think too much before adding this herbal immunity booster to your diet plan. This powder is free from harmful preservatives and additives to ensure that the goodness of giloy is not reduced.
You can boil this powder in water along with tulsi and other herbal ingredients to make your immunity booster drink whenever you want.
This pack of giloy powder can be another affordable choice to consider for your immune system and overall health. This powder is made from the leaves of the giloy plant and can even help you reduce stress and anxiety to an extent. So, you can use it as an immunity booster and stress-buster.
Store this giloy powder in an airtight container to avoid the loss of nutrients or contamination due to exposure to dust, moisture or pollutants.
This giloy powder can be another affordable immunity booster that you can buy online. This powder is made from the stem of the giloy plant to give you plenty of nutrients and allow you to prepare various immunity booster drinks easily at home. Available in a zip-lock pouch, it is easy to store this giloy powder at home.
You can have 1 spoon of powder with water as per the instructions of your doctor to boost your immunity.
BIRMINGHAM, Ala. (WBRC) – New research from Johns Hopkins University Hospital shows a third dose of the COVID-19 vaccine could be a way to improve immunity in immunocompromised patients, especially for organ transplant recipients.
Health experts said solid organ transplant recipients tend to have weakened immune systems.
“When you have an organ transplant, you get put on very powerful drugs to suppress your immune system because it’s your immune system that can otherwise lead you to reject those organs that you’ve received, and therefore when they’re given a vaccination, the vaccine doesn’t induce immunity. It doesn’t create an immune response,” said State Health Officer for the Alabama Department of Public Health, Dr. Scott Harris.
But a new study from Johns Hopkins University Hospital shows a third dose of the COVID-19 vaccine could improve immunity response in these groups.
“We’ve had these people with immune system problems like organ transplant patients who are allowed to take a vaccine, but whom we really didn’t expect the vaccine to work, and so, it’s encouraging to that perhaps there is a way to induce immunity in these patients,” Dr. Harris said.
The study followed 30 solid organ transplant recipients.
Almost all of them had low or no immunity to the vaccine.
But after a third shot, 33% of patients with no immunity, and 100% of patients with low immunity, increased their antibody levels.
“We also know that because of their medical conditions, in many cases, they’re at even more risk of serious illness if they do get COVID compared with the average person. We want to protect them even more, in a way, than the average person. So, it’s encouraging to think that we may have a way to do that,” Dr. Harris said.
Health experts said this 30-patient study isn’t big enough to be a formal patient trial, but it’s enough preliminary data to show promise in future studies.
They still recommend organ transplant recipients get the vaccine, but still take precautionary measures to ensure protection.
Pharmacist Katie McDonough reconfigures the Pfizer-BioNTech vaccine when filling syringes at the UMass Memorial Healthcare COVID-19 Vaccination Center at the Mercantir Center in Worcester on April 22, 2021. Joseph Prezioso AFP
A small new study offers a faint hope that organ transplant recipients can be given a third dose of the COVID-19 vaccine to enhance their defense against coronavirus.
It’s important Previous studies show Almost half of organ transplant recipients showed no antibody response after two doses of Pfizer or modelna vaccine.
And even transplant recipients who responded antibody to vaccination were often more modest than those with a healthy immune system. Therefore, doctors advise these patients not to assume that vaccination is equivalent to immunity. According to the Scientific Registry of Transplant Recipients, more than 400,000 people in the United States have undergone organ transplants.
They found that one-third of patients who did not have previously detectable antibodies showed increased antibody levels after the third dose. And all patients who previously showed low levels of antibody after two doses of vaccine showed high levels of antibody after the third dose.
“For everyone involved [these are] A promising finding that the defensive immunity of immunosuppressed people may ultimately be reached, “said Dr. Dolly Segev, a transplant surgeon and study author at Johns Hopkins Medicine... Although the findings are preliminary, he says, they are consistent with previous studies of how transplant recipients respond to other vaccines.
Researchers say this is the first study to report a response to a third vaccination. In this observational study, they tracked group transplant recipients who asked for a third dose on their own and tested antibody levels after dosing.
Researchers say their findings support the use of clinical trials to determine whether transplant recipients should receive the COVID-19 vaccine booster as part of standard clinical care. If the findings are reproduced in a larger study, they may affect some other types of immunocompromised patients.In fact, in France Health officials already recommend Patients with severe immunodeficiency, such as organ transplant patients and dialysis patients, receive a third dose of Pfizer or modelna vaccine.
Segev says he expects more data from France to come from France regarding the effectiveness of a third dose in immunocompromised patients.
“Obviously, all we need to learn is … who responds to the third dose,” he says. “People who need changes other than the third dose,” such as temporary changes in immunosuppressive drugs to improve the antibody response to vaccination.
Segev and his colleagues are currently seeking regulatory approval to give transplant recipients a third dose of the vaccine and initiate an intervention study that can monitor their response. They hope to be able to register participants next month or two months.
But for now, “the best we can all do for immunosuppressed people is that our normal immune system can protect vulnerable friends and family among us who have suppressed the immune system. So, get all the vaccinations, “he says.
Third dose of COVID vaccine may boost immunity of transplant recipients-WUSF public media
Source link Third dose of COVID vaccine may boost immunity of transplant recipients-WUSF public media
Giloy or Tinospora Cordifolia is a medical plant belonging to herbal vines that grow in the tropical regions of the Indian subcontinent. Giloy has been used for centuries in India and around the world to treat various ailments. In Ayurveda, Giloy is considered to be one of the best medicines to control and reduce various fevers and other ailments. Giloy has been called an ‘Amrit’ or Immortal plant in Ayurveda because of its high immune-boosting and other medicinal properties. Before understanding how to use giloy to boost your immunity, it is important to understand the medicinal properties of this plant.
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Medicinal properties of Giloy Giloy is effective against ailments such as diabetes, neurological problems, fevers such as hay fever, dengue fever, and chronic fever. The giloy plant also helps people in lowering their anxiety and stress levels by cleaning the body from toxins. The stem of giloy plants is considered to have the most nutritional value. It is advised to take giloy in powdered form or in the form of kadha (decoction) or even juice. The dosage of giloy would depend on the level of ailment.
How to make giloy juice at home? Get some freshly cut stems of the giloy plant and blend them well with water in a blending machine to obtain giloy paste. Dilute the paste and sieve it to obtain giloy juice. The juice should be consumed as per your general physician’s advice. Giloy can also be taken in powdered form and tablets
Here is a guide for you on how to use giloy to boost your immunity.
Uses of Giloy
Anxiety and Stress Reliever
Using Giloy for boosting immunity
Giloy herb is rich in alkaloids, glycosides, steroids, and other compounds that activate the immune system and increase vitality in a person. To boost your immunity, mix it with a small amount of water, you can refer to your general physician about the required dosage. It is advisable to take giloy juice twice daily before meals.
This giloy juice is added with neem and tulsi that are known for their antimicrobial properties and medicinal properties respectively. Giloy and neem together cleanse the liver which is responsible for getting rid of toxins from your body. This juice can be consumed twice a day before meals or as advised by your physician. Tulsi furthers cleanses and rebuilds cells of the body.
Giloy can be used in the treatment of various fevers including chronic, dengue, malaria, and hay fevers. Fever generally happens due to two reasons – remaining toxins in the body from food and water or due to the entrance of foreign pathogens.
Giloy is rich in javarghana which has properties to fight and reduce fever. Similarly, giloy has anti-inflammatory properties that attack the cause of the fever and helps the body retain normal temperature.
To reduce fever, one can be given giloy juice or giloy kadha. Alternative use could be to mix giloy powder with few drops of honey and have it as advised by the doctor.
This giloy powder helps in correcting imbalances in the body that lead to problems such as burning sensation of hand and feet, allergy, skin inflammation, and acidity. The powder is directly obtained from the giloy plant and has no added preservatives. Use the powder with water or honey for best results
Giloy enhances the production of insulin in the body, insulin controls the level of sugar in the body. High sugar levels can lead to ulcers and kidney problems. Use giloy powder with half a glass of warm water in the morning and at night.
This is a pack of 60 vegetarian capsules that can be consumed twice as per the instructions of your doctor. These capsules can be taken with warm water in the morning or at night, as advised by your doctor. Giloy capsules also help in liver function by regulating enzymes and metabolism.
Giloy regulates metabolism in the body that aids the entire food eating and digestion process. It is useful in treating acidity, vomiting, colitis, and various other problems such as nausea, diarrhea.
You can take half a spoon of giloy juice with half a glass of lukewarm water in the morning and at night to reduce stomach and gut-related ailments. Use Giloy for anxiety and stress relieving
Giloy is also used to treat anxiety and stress. The plant contains antioxidants that clear the body of toxins, it calms down your body and mind as well. The herbal plant also improves the cognitive behavior of the person. Use half a spoon of the giloy juice with the same amount of water on an empty stomach in the morning to have a peaceful and anxiety-free day. If you have anxiety then the below-mentioned guide can be referred to help in anxiety and stress relief at home.
Can five-year-old children be given giloy juice? Yes, it can be given to five-year-old children upon the advice of the doctor.
What is better- giloy juice and powder or tablets? If you are looking for instant giloy usage then giloy juice and powder are better. However, if you are looking for long-term usage of giloy then it is advisable to consume giloy tablets.
Is giloy good for hair? Yes, giloy contains antioxidants properties that are good for hair strength and scalp care.
DISCLAIMER: The Times of India’s journalists were not involved in the production of this article.
New Delhi: Immunity in Covid-recovered patients is long-lasting and gets a 50-fold boost after vaccination, according to a new study.
The study, published in the journal Nature Monday, also said that the mRNA vaccines can sufficiently protect against emerging mutations.
More than a year after the Covid-19 pandemic broke, the emergence of new variants that appear to be more transmissible and resistant to antibodies has added to the challenge of controlling the spread of the disease.
To understand how long the immunity lasts, researchers from the Rockefeller University, Weill Cornell Medicine and California Institute of Technology assessed the blood samples of 63 people who had recovered from Covid-19. The samples were collected 1.3, 6.2 and 12 months after infection.
Of these 63 people, 41 per cent had received mRNA vaccines.
The study found that in Covid-recovered patients, antibodies against the protein known as receptor binding domain (RBD) of SARS-CoV-2 and neutralising activity remain relatively stable from six to 12 months, without vaccination.
A receptor-binding domain is a key part of the virus located on its ‘spike’ protein that allows it to latch onto the cell to gain entry into cells and lead to infection.
Memory B cells — a type of white blood cells that learn to recognise specific viral proteins — was also found to remain stable upto 12 months.
In addition, the team found that vaccination increases all components of the antibody response. Antibody levels remained relatively unchanged between six to 12 months after SARS-CoV-2 infection, and that vaccination further boosted this activity by nearly 50-fold.
The study found that the ability of vaccine-induced antibodies to neutralise variants of concern was comparable to or greater than that against the original virus.
Researchers also identified that the broad response against the SARS-CoV-2 virus involves what is known as the antibody somatic mutation — a cellular mechanism using which the body’s immune system adapts to the changing virus during the course of the infection.
This results in antibodies that are exceptionally resistant to mutations in the SARS-CoV-2 RBD — including those found in variants of concern
In addition, B cells that produce a broad range of potent antibodies are retained in the body over time and expand dramatically after vaccination.
The data suggest that immunity in Covid-recovered individuals will be very long-lasting, researchers said. Along with this, Covid-recovered patients who receive mRNA vaccines produce antibodies and memory B cells that should be protective against circulating SARS-CoV-2 variants, the study concluded.
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Healthy eating is a crucial part of strengthening the immune system. Having nutrient-rich foods daily is the easiest way to build immunity naturally. There are several foods loaded with essential micronutrients that can be easily included in the diet and jackfruit is one of them.
The sweet-smelling, succulent summer fruit can be eaten raw or either can be cooked. Most people relish the juicy flesh and discard the hard nut-like seeds, unaware of the fact that the seeds are loaded with nutrients and can help to boost immunity. Recently, celebrity nutritionist, Rujuta Diwekar took to her Instagram handle and shared the benefits of this delicious summer fruit.
Why Rujuta suggest eating jackfruits
As per Rujuta, eating diverse foods and leading a disciplined lifestyle is the foundation of building immunity. The food you eat should not be exotic or expensive. Even the seasonal and local fruits or veggies available in your region are loaded with healthy nutrients and can protect against health ailments.
The mighty seeds of jackfruits can be cooked as curry or roasted with some salt and pepper and can be consumed as snacks. Packed with diverse kinds of nutrients, this fruit can help you in more than one way. Rich in different kinds of nutrients, jackfruits add diversity to your diet and strength to your tissues.
Nutrient content of jackfruits
Jackfruit contains a moderate amount of calories and is rich in fiber. One cup of sliced fruit contains:
Carbs: 40 grams
Fiber: 3 grams
Protein: 3 grams
Vitamin A: 10% of the RDI
Vitamin C: 18% of the RDI
Magnesium: 15% of the RDI
Potassium: 14% of the RDI
Copper: 15% of the RDI
Manganese: 16% of the RDI
The fruits are also rich in protein and have only a small amount of fat. The antioxidant present in the yellow fruit is mostly attributed for its potential health benefits. Apart from this, the fruit also contains a small amount of all the essential nutrients.
Jackfruit and immunity
This seasonal fruit is loaded with vitamins A and C, which may prevent several illnesses. Eating this fruit regularly may also reduce the risk of viral infections. Vitamin C may help to prevent inflammation and cut down the risk of chronic diseases like heart disease and cancer. The two main antioxidants- Carotenoids and flavonoids can help to lower inflammation, decrease the risk of type 2 diabetes, heart disease and high blood pressure.
Other benefits of jackfruits The yellow summer fruit can also improve skin condition and slow down ageing. The antioxidants present in it may protect your cells from oxidative stress and inflammation, caused due to free radicals. It is even used in several places for treating health ailments like asthma, diarrhea and stomach ulcers.
Patients with kidney failure are at increased risk for SARS-CoV-2 infection making effective vaccinations a critical need. It is not known how well mRNA vaccines induce B and plasma cell responses in dialysis patients (DP) or kidney transplant recipients (KTR) compared to healthy controls (HC). We studied humoral and B cell responses of 35 HC, 44 DP and 40 KTR. Markedly impaired anti-BNT162b2 responses were identified among KTR and DP compared to HC. In DP, the response was delayed (3-4 weeks after boost) and reduced with anti-S1 IgG and IgA positivity in 70.5% and 68.2%, respectively. In contrast, KTR did not develop IgG responses except one patient who had a prior unrecognized infection and developed anti-S1 IgG. The majority of antigen-specific B cells (RBD+) were identified in the plasmablast or post-switch memory B cell compartments in HC, whereas RBD+ B cells were enriched among pre-switch and naïve B cells from DP and KTR. The frequency and absolute number of antigen-specific circulating plasmablasts in the cohort correlated with the Ig response, a characteristic not reported for other vaccinations. In conclusion, these data indicated that immunosuppression resulted in impaired protective immunity after mRNA vaccination, including Ig induction with corresponding generation of plasmablasts and memory B cells. Thus, there is an urgent need to improve vaccination protocols in patients after kidney transplantation or on chronic dialysis.
COVID-19 leads to a high morbidity and mortality especially among patients with kidney failure (1). Dialysis patients (DP) and kidney transplant recipients (KTR) are at increased risk of developing COVID-19 and experiencing a severe infection, due to exposure risk in the health care system, their co-morbidities, and their impaired immune function from kidney failure or immunosuppressive medications. For this vulnerable population, vaccination is of the utmost importance.
The mRNA SARS-CoV-2 vaccine BNT162b2 (BioNTech/Pfizer) has demonstrated efficacy in healthy individuals in a clinical study (2) and under real-world conditions (3). Recent data described a lower serological response to an mRNA vaccine in dialysis patients (4) and kidney transplant recipients (5), suggesting an overall diminished vaccine response. Whereas numerous studies have addressed the consequences of conventional vaccines on B and plasma cells (6–8) and corresponding Ig levels, nothing is known yet about the B lineage consequences in response to an mRNA vaccine among healthy controls and immunocompromised patients. The ongoing uremic state in kidney failure patients leads to an immune dysfunction on various levels of innate and adaptive immunity. Restoring kidney function by kidney transplantation does not fully restore cellular and adaptive immunity while immunosuppressive drugs impair protective immunity further. Thus, kidney failure patients (with or without kidney transplant) show an increased susceptibility for infection and viral-associated cancers (9–11).
Previous studies in kidney failure patients (with or without kidney transplant) report markedly diminished response to vaccinations. This has led to an adaption of vaccination protocols with either higher initial vaccine doses or more frequent booster doses (12, 13). If such adaptations of the protocol are required for the COVID-19 mRNA vaccines or if alternate adjuvanted vaccines are necessary is not yet known.
The induction of B cell memory by mRNA vaccines and the relation to humoral immune response is largely under-investigated, especially studies of immunocompromised cohorts. Upon natural acute SARS-CoV-2 infection, immunological memory (antibodies and memory B cells) is shown to last for at least 8 months (14–16). In patients with chronic kidney disease, such data are largely lacking, although prolonged time of viral shedding with impaired virus clearance is reported and likely related to impaired cell-mediated immunity (17).
In this study, we compared the characteristics of the humoral and antigen-specific B cell immune response against the mRNA vaccine BNT162b2 between healthy controls and patients with kidney failure treated by maintenance hemodialysis or kidney transplantation. We found a diminished humoral response to BNT162b2, and a lack of proper B lineage memory formation including RBD-specific plasmablasts and post-switch memory B cells.
Cohorts and patient characteristics
For this study, we recruited 35 healthy controls (HC), 41 patients on maintenance hemodialysis, 4 peritoneal dialysis patients and 40 KTR. Hemodialysis and peritoneal dialysis (PD) patients did not significantly differ in age and vaccine response and were therefore grouped together. After written informed consent, serum and peripheral blood mononuclear cells (PBMCs) were collected before vaccination (baseline) and 7 ± 2 days after boost vaccination (second dose), respectively. Serological follow-up was available in DP and KTR patients 3-4 weeks after boost. Due to local vaccination guidelines, HC, who were mainly health care workers, were significantly younger than DP (p< 0.01). DP were significantly older than KTR. As known for patients with kidney failure (18), a majority of DP and KTR were male. The median time on dialysis was 5.5 years (IQR, 2.0, 9.0). Among KTR only one patient was transplanted less than one year ago and median time after transplantation was 5.0 years (IQR. 2.0, 10.0). KTR were on a uniform immunosuppressive regimen with mycophenolate mofetil (MMF) in 39/40, steroid in 37/40 and calcineurin inhibitor (CNI) in 37/40 patients. Demographics are summarized in Table 1. To identify previously SARS-CoV-2 infected individuals we measured anti-nucleocapsid protein (NCP) antibodies 7 ± 2 days after boost, which is not a component of BNT162b2. Therefore, positivity of NCP originated from natural infection. One HC, one DP and one KTR were identified anti-NCP positive (Figure S1).
Table 1Patient characteristics.
Substantially impaired serological response upon mRNA vaccination with BNT162b2 in DP and even more pronounced in KTR patients
Antibody response to BNT162b2 was assessed in all individuals 7 ± 2 days after boost using the Euroimmun ELISA for the detection of IgG and IgA against the S1 domain of the SARS-CoV-2 spike. All HC seroconverted, were positive for both anti-S1 IgG and anti-S1 IgA (Fig. 1 A, B), and showed SARS-CoV-2 neutralization (Fig. 1C). Anti-S1 IgA and anti-S1 IgG titers were markedly diminished 7 ± 2 days after boost in DP patients compared to HC (Fig. 1A, B). In the S1 IgG assay, 31/44 (70.5%) of the DP were positive and 30/44 (68.2%) developed anti-S1 IgA antibodies.
Of particular interest, anti-S1 IgG and anti-S1 IgA responses were substantially diminished in KTR compared to HC and DP, respectively. Only one out of 40 patients (2.5%) was positive for IgG (apparently after prior unrecognized infection) and 4 patients for IgA (10%). Virus neutralization was observed in 30/44 (68.2%) DP patients (Fig. 1C), while 0/40 KTR had inhibiting antiviral antibodies (Fig. 1C). Interestingly, the patient’s serum with IgG and prior infection did not achieve neutralizing effects. Previously infected individuals are indicated in red in (Fig. 1A-C). Their levels of antibody and neutralization was in the range of other individuals of the respective group.
To further address the effect of age in our cohort, we divided the group into individuals <60 years and >60 years of age. HC >60 years showed a lower anti-S1 IgG and IgA than HC <60 years, while their neutralization capacity was unchanged (Fig. 1D-F). DP and KTR did not show differences in anti-S1 IgG and IgA, but DP >60 exhibited a lower neutralization capacity compared to DP<60 years (Fig. 1D-F). DP and KTR <60 and >60 years of age showed an overall diminished anti-S1 IgG and IgA as well as neutralization capacity compared to HC<60 and >60 years of age, respectively (Fig. 1D-F). Anti-S1 IgG and IgA correlated with age in HC while this correlation was weak in DP and KTR (Figure S2).
HC showed no significant further increase of humoral response later than 28 days post initial vaccination with BNT162b2 (19). A delayed immune response might have explained the initial limited serologic response in immunocompromised individuals (DP and KTR) with mRNA vaccines. Therefore, we collected additional follow-up samples from KTR and DP 3-4 weeks after boost. Interestingly, anti-S1 IgG increased significantly in DP (Fig. 1G), while anti-S1 IgA and surrogate neutralization remained stable (Fig. 1H) during the additional observation. In contrast, KTR patients did not develop additional anti-S1 IgG, anti-S1 IgA and neutralizing antibodies until the second follow-up investigation 3-4 weeks after the boost (Fig. 1G-I). In summary, KTR showed a significantly reduced serological response including lack of further increases up to 3-4 weeks after BNT162b2 boost.
DP and KTR showed reduced B cells numbers but similar distribution among memory subsets
B cell lymphopenia is described for DP (20) and KTR (21) and might affect proper humoral immune responses. To initially address the frequency, distribution, and phenotype of peripheral blood B cells in DP, KTR compared to HC, we analyzed the distribution of B cell subsets at baseline (pre-vaccination) and 7 ± 2 days after boost (Fig. 2A). Of interest, the frequency of CD19+ B cells was significantly diminished only in KTR compared to DP at the assessment 7 ± 2 days after boost and compared to HC at baseline, while no differences were otherwise observed (Fig. 2B). However, substantial reductions in absolute B cell counts were identified between KTR patients and HC at baseline as well as HC versus the DP and KTR cohorts, 7 ± 2 days after boost, respectively (Fig. 2C).
The frequency of plasmablasts among total CD19+ B cells did not differ between groups (Fig. 2D, E) at baseline and after boost. DP and KTR patients carried lower frequencies of pre-switch B cells, while KTR had an increased frequency of naïve B cells before vaccination but not after vaccination. Post-switch memory B cells were higher in DP before but not after vaccination. Double negative (DN, CD27-IgD-) B cells did not differ significantly among groups (Fig. 2D,E). Interestingly, immunoglobulin isotype distribution among B cell subsets was not different among study groups (Fig. 2F,G). In summary, KTR and DP showed a characteristic reduction of absolute B cells with certain differences in the pre-memory (naive and pre-switch) but no differences within B memory compartments.
Impaired induction of anti-BNT162b2 B cell and plasmablast responses in KTR and HD patients
In order to better understand the underlying B and plasma cell differentiation upon vaccine challenge, we developed a flow cytometric method to identify and quantify RBD-specific B cells in human peripheral blood. B cells (CD3−CD14−CD19+) able to bind simultaneously RBD-AF488 and RBD-AF647 were validated as antigen-specific (Fig. 3A). The specificity of RBD binding was further confirmed by blocking with unlabeled RBD prior to staining (Fig. 3A). We identified an RBD-specific clone (CDRH3: ARDYGGNANYFHY, CDRL3:QQYDNLPIT) in 3 different vaccines (HC) with highly identical amino acid sequence as reported before upon mRNA vaccinations (22). Subsequently RBD+ B cells were further analyzed according to their distribution among subsets and isotypes (gated as shown for general B cells in Fig. 2A,F.
Overall, an increased frequency of RBD-specific B cells among CD19+ B cells was found 7 ± 2 days after boost compared to baseline for HC, DP and KTR (Fig. 3B). The absolute number of antigen-specific B cells was significantly increased in HC at 7 ± 2 days after boost only in contrast to DP and KTR patients (Fig. 3C).
Subsequent analyses addressed the distribution of the RBD-specific B cells among B cell subsets (gating as seen in Fig. 2A). Most notably, a large number of RBD+ B cells were found in the plasmablast compartment in HC, which was significantly lower in DP and KTR (Fig. 3D and Figure S3). The very limited antigen-specific B cells in KTR resided preferentially within the naïve and pre-switch compartment compared to HC (Fig. 3D and Figure S3). In contrast, antigen-specific B cells from HC were detected mainly within post-switch and double negative B cells belonging largely to the memory compartment (Fig. 3D). Consistent with impaired (not completely executed) B memory induction, the frequency of IgM RBD+ B cells (defined as IgG-IgA-) was more frequently detected in KTR and DP patients compared to HC, in whom antigen-specific IgG+ B cells dominated. The frequency of IgA+ RBD+ B cells was comparable across groups (Fig. 3E).
Two-dimension t-SNE plots clustering all RBD+ B cells according to expression patterns, analyzed with a color axis for CD27, CD38 and IgG, illustrated the notable differences between groups including the substantially reduced plasmablasts (CD27++, CD38++) and IgG expressing RBD+ B cells in the KTR cohort (Fig. 3F). In summary, KTR patients were not only characterized by a reduced overall number of antigen specific B cells, but also exhibited signatures of abnormal B cell memory formation.
Unique correlation of anti-BNT162b2 serological and B cell responses
Our earlier vaccination studies against tetanus, diphtheria and KLH (Keyhole Limpet Hemocyanin) do not reveal a typical relation between plasmablast/ B cell responses and the serologic Ig outcome (6–8) in contrast to such relation for polysaccharides, such as meningococcal and pneumococcal vaccine (23, 24). Therefore, we wondered how the anti-BNT162b2 humoral immune and B cell specific responses against an mRNA vaccine are interrelated. A correlation matrix including all groups and patients was carried out. As previously described (25, 26), the neutralization capacity strongly correlates with anti-S1 IgG as well as anti-S1 IgA (Fig. 4A). The frequency of total RBD+ cells did not correlate with anti-S1 IgG, IgA and neutralization capacity, respectively. The frequency and total number of RBD+ plasmablasts correlated with all parameters of humoral response (anti-S1 IgG, anti-S1 IgA and the neutralization capacity). Age and the total number of RBD+ B cells correlated in HC, while it did not in DP and KTR (Figure S2). Subsequent analyses addressed how non-responders with a negative neutralization test (<30%) differed from responders (>30%). Responders and non-responders were significantly different in the frequency and number of RBD+ plasmablasts and RBD+ pre-switch memory B cells as well as in the frequency of RBD+ naïve B cells (Fig. 4B). This data suggested clear interdependence of the distinct memory B and plasmablast compartments being a characteristic of this mRNA vaccine.
Diminished T cell and plasmablast response in KTR
To further understand the lack of B cell memory induction, we sorted CD27++CD38++ plasmablasts, CD27+CD38var memory B cells and HLA-DR+CD38+ activated T cells of the peripheral blood as indicators of the ongoing immune response after vaccination (7, 27) and generated single cell transcriptomes combined with Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) (28) for selected surface markers (Figure S4) 7 ± 2 days after boost vaccination. After removal of doublets, we analyzed a total of 10796 cells. According to their transcriptomes, these cells were categorized in 7 different clusters as shown by Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP) (29) (Figure S4A, B). We focused on the most abundant clusters. Four of which belong to the T cell compartment, with the most abundant cluster 0 having represented activated CD8+HLADR+MS4A1+ T cells, followed by cluster 1 which represented different types of the CD4+ T cells, including e.g., FOXP3+CD25+ regulatory T cells (Figure S4C and S5). Cluster 2 contained different populations of CD8+ T cell expressing either CD45RA or CD45RO (Figure S4B,C) and finally cluster 5 represented a TCF7+CD27+GZMK+ T cells. Cluster 6 contained proliferating cells expressing MKI67 (Figure S4B-C). Memory B cells expressing high levels of MS4A1, HLA-DRA and CD27 were located in cluster 3. Cluster 4 represented plasmablasts expressing CD27, CD38, PRDM1 and IRF4 (Figure S4B-C). Of note, the protein expression of selected surface markers detected by CITE-seq supported the classification of the 7 main clusters (Figure S5). In the selected cohort of 4 KTR, 3 did not show a serological response to the vaccination (non-responder), while one individual had detectable anti-S1 IgG antibodies but also a previously undetected infection (responder). Accordingly, the 3 non-responders had reduced frequencies of cluster 4, 5 and 6 representing plasmablasts, TCF7+CD27+GZMK+ T cells and proliferating MKI67-expressing lymphocytes (Figure S4D, E). CD45RO+ follicular T helper like cells expressing either IL21 or PDCD1+ could only be detected in the CD4+ T cell compartment (Cluster 1) of the non-responder #3 and the responder (Figure S4F). Interestingly, the majority of memory B cells (cluster 3) of the responder expressed ITGAX (gene encoding for CD11c), while this subpopulation in cluster 3 was almost absent in the non-responders (Figure S4F).
SARS-CoV-2 mRNA vaccines are highly protective against COVID-19 (2, 30), while it is not yet clear how these vaccines induce and maintain B cell memory responses among immunocompromised patients. Available data show a durable humoral response and B cell response (31, 32) in healthy individuals and also elderly patients (2, 19). Moreover, mRNA vaccines are reported to induce germinal center (GC) responses in mice and are expected to result in lasting plasma cell responses (33). Here, we investigated the distribution of anti-BNT162b2 antigen-specific B cell responses among HC in comparison to DP and KTR as prototypes for differentially immunocompromised patients. An assay for the detection of RBD-specific B lineage cells has been developed with high specificity based on our prior experiences for the detection of antigen-specific B cells and plasmablasts (i.e., tetanus, KLH, pentraxin (8, 34)). Specificity was proven by appropriate blocking experiments and identification of an RBD-specific clone (CDRH3) among RBD++ B cells, which was found in 3 different vaccines (HC) with highly identical amino acid sequence immunized as reported very recently upon mRNA vaccinations (22). Of particular interest, seroconversion and the induction of neutralizing antibodies upon BNT1622b vaccination was very robust and similar in our cohort in HC as observed by prior studies (2). In these HC, we also found a typical formation of antigen-specific plasmablasts and post-switch memory B cells upon vaccination boost which was comparable to frequencies of tetanus-specific B cells after booster vaccination (35). Thus, the findings among HC provide a valid comparison with the two patient cohorts.
Among DP and KTR, we observed a markedly diminished generation of antigen-specific B cells, especially within major effector compartments of protective B cell immunity, namely plasmablasts and memory B cells. Consistently, lower IgG+ anti-RBD cells were found related to impaired induction of a vaccine response. This was accompanied by a low rate of seroconversion of DP on day 7 ± 2 that somewhat improved 3-4 weeks after vaccination, while this could not be compared to HC in our cohort due to a missing follow-up. In the KTR cohort, the rate of serological and cellular response was almost absent with only one patient who developed specific anti-S1 IgG but apparently based on a prior unrecognized infection and likely reflecting a further boost underlining the potential effectiveness of optimized vaccines or vaccination protocols. Interestingly, no KTR patient exhibited a positive neutralization at day 7± 2 after boost including the patient with positive IgG titers. At a further follow up 3-4 weeks after boost, no seroconversions were found in KTR. These data are in contrast to recently published data of Boyarsky et al. who described a seroconversion in 23/223 (10.35%) of KTR vaccinated with BNT162b2 already after the first dose (5). As a limitation of our study, we only have a limited sample size as well as a very uniform immunosuppressive regimen of KTR, which does not allow for a firm conclusion which immunosuppressant may cause the impaired immune response. For DP patients, seroconversion rates of about 90% after two doses have been described which is similar to the findings in our cohort (4, 36).
The large discrepancy of the serological response and impaired B cell response in our KTR cohort raises the question about which factors or mechanism are involved. Incorrect handling of the sensitive mRNA vaccine can be excluded since the same mRNA vaccine of the same lot induced a favorable response among DP patients. The major difference between KTR and DP/HC appeared to be the almost uniform immunosuppressive therapy with MMF, CNI and glucocorticoids among the KTR patients, although the individual impact of MMF, cyclosporine vs. tacrolimus and glucocorticoids needs to be further delineated. CNI and MMF directly inhibit activation and proliferation of CD4+ T cells, Tfh cells and B cells (37–41). In this regard, single cell transcriptomes and CITE-seq analyses identified substantial differences between the vaccine responder and three non-responders within the KTR cohort. Namely plasmablasts, TCF7+CD27+GZMK+ T cells and proliferating MKI67-expressing lymphocytes were increased in the responders suggesting that these three subsets are key drivers of a successful BNT162b2 response.
Three individuals with likely prior asymptomatic virus exposure (each in HC, DP and KTR cohorts) were identified by preexisting antibodies against viral NC. Interestingly, they did not show notable differences in vaccine response compared to their cohorts, with the exception of one seroconversion in the KTR. A number of recent studies report that a first vaccination in previously infected individuals acts as a boost that leads to higher antibody levels than individuals vaccinated twice with an mRNA vaccine. It further does not change isotype distribution among memory B cells (32, 42, 43). After a natural COVID-19 infection the numbers of RBD-specific memory B cells of healthy individuals are similar to those of patients who recovered from natural COVID-19 infection, while levels of anti-S1 and anti-RBD IgG are significantly higher in vaccinated individuals (44). Interestingly, the clonality of IGLV genes among RBD+ is very comparable between natural infection and the mRNA vaccination (44). At the moment it is not known whether the magnitude of antibody levels or the presence or magnitude of a T cell response, or both, correlate with the protection against symptomatic COVID-19. However, after natural COVID-19 infection the presence of anti-spike antibodies protects from recurrent infection, while a previous infection without detectable antibodies does not (45). Initial observational data from Israel indicate that CKD as well as immunosuppression have a negative impact on vaccine efficacy (46), which indicates that impaired B cell memory also results in diminished protection.
Interestingly, we found a unique relationship between plasmablast response and Ig titers which is not seen in tetanus and KLH vaccination (6–8) and is only described for polysaccharide and protein-polysaccharide conjugate vaccinations (47). Polysaccharide vaccines in contrast to mRNA vaccines induce certain serological responses following vaccination in KTR (48) which possibly relates to T independent responses. In this context, our single cell analysis confirmed a diminished plasmablast induction in the non-responders (KTR) but importantly also lack of proper CD4 and CD8 T cell activation. In the responder, classical signs of vaccine response with simultaneous B and T cell activation occurred but insufficient to induce neutralizing antibody titers. KTR have to be considered as a patient group who remains vulnerable to SARS-CoV-2 infection, even if vaccinated with the currently established BNT162b2 vaccination scheme.
In summary, we described a diminished humoral response to BNT162b2 as well as lack of appropriate memory formation including RBD-specific plasmablasts and post-switch memory B cells in DP and KTR. DP were able to further mature their antibody response in contrast to KTR. As such, optimized vaccination strategies especially for KTR patients are needed to achieve adequate antiviral protection.
MATERIALS AND METHODS
The study was designed to investigate the sero-response (anti-S1 IgA, anti-S1 IgG levels and neutralization test) and B cell memory formation in DP and KTR after vaccination with BNT162b2. HC, KTR and DP were vaccinated with BNT162b2 21 days apart. Baseline blood was drawn to identify previously infected individual (NCP ELISA, anti-S1 IgA, anti-S1 IgG levels) and access baseline B cell phenotype of HC, DP and KTR (flow-cytometry). To investigate the plasmablast response peripheral blood samples were obtained 7 ± 2 days after boost vaccination. B cell subtypes as well antigen-specific B cells were analyzed by flow-cytometry. Seroresponse was investigated 7 ± 2 days (HC, DP, KTR) and 3-4 weeks after the second dose (DP, KTR).
Peripheral blood samples (EDTA anti-coagulated or serum-tubes, BD Vacutainersystem, BD Diagnostics, Franklin Lakes, NJ, USA) from 35 healthy controls, 40 hemodialysis patients, 4 peritoneal dialysis patients and 40 kidney transplant recipients were collected at 7 ± 2 days after the second dose of SARS-CoV-2 BNT162b2 vaccination. Individuals of KTR and DP are in part also represented in published manuscripts (serological response only) (49, 50). Material before vaccination was available for 19 healthy controls, 21 hemodialysis patients, 2 peritoneal dialysis patients, and 28 kidney transplant recipients, while a follow up after 3-4 weeks after boost is available for currently for 26 KTR and 37 DP. Donor information is summarized in Table 1. All participants gave written informed consent according to the approval of the ethics committee at the Charité University Hospital Berlin (EA2/010/21, EA4/188/20), the ethics committee of Saxony-Anhalt (EA7/21) and the ethics committee of the University of Greifswald (BB019/21).
Sample processing and isolation of peripheral blood mononuclear cells (PBMCs) and staining
Serum tubes were centrifuged at 3000rpm for 10 min to separate plasma. Serum was stored at -20C for antibody analysis. PBMCs were prepared by density gradient centrifugation using Ficoll-Paque PLUS (GE Healthcare Bio-Sciences, Chicago, IL, USA). For staining 1-3 × 106 cells were suspended in 50 μl of PBS/0.5% BSA/EDTA and 10 μl Brilliant Buffer (BD Horizon, San Jose, CA, USA. Cells were stained for 15 min on ice and washed afterwards with PBS Dulbecco containing 1% FCS (fetal calf serum, Biowest, Nuaillé, France) (810 xg, 8 min, 4°C). Flow cytometric analysis was performed as indicated in the Figs. 1–4.
All flow cytometry analyses were performed using a BD FACS Fortessa (BD Biosciences, Franklin Lakes, NJ, USA). To ensure comparable mean fluorescence intensities (MFIs) over time of the analyses, Cytometer Setup and Tracking beads (CST beads, BD Biosciences, Franklin Lakes, NJ, USA) and Rainbow Calibration Particles (BD Biosciences, Franklin Lakes, NJ, USA) were used. For flow cytometric analysis, the following fluorochrome-labeled antibodies were used: BUV737 anti-CD11c (BD, clone B-ly6, 1:50), BUV395 anti-CD14 (BD, clone M5E2, 1:50), BUV395 anti-CD3 (BD, clone UCHT1, 1:50), BV786 anti-CD27 (BD, clone L128, 1:50), BV711 anti-CD19 (BD, clone SJ25C1,1:25), BV605 anti-CD24 (BD, clone ML5, 1:50), BV510 anti-CD10 (BD, clone HI10A, 1:20), BV421 anti-CXCR5 (BD, clone RF8B2, 1:20), PE-Cy7 anti-CD95 (ThermoFischer, Waltham, MA, USA clone APO-1/Fas, 1:100), PE-CF594 anti-IgD (Biolegend, San Diego, CA, USA, clone IA6-2, 1:5000), APC-Cy7 anti-CD38 (Biolegend, clone HIT2, 1:1000), PE-Cy7 anti-IgG (BD, clone G18-145, 1:1000), anti-IgA-Biotin (BD, clone G20-359, 1:50), BV650 anti-IgM (BD, clone MHM-88, 1:50), FITC anti-HLA-DR (Biolegend, clone L234, 1:25), PE anti-CD21 (BD, clone B-ly4, 1:25), APC anti-CD22 (BD, clone S-HCL-1, 1:25). Siglec-1 (CD169, 1:25) expression analysis on CD14+ monocytes was performed at baseline and at the follow-up time-point as previously described (11). Number of absolute B cells was measured with Trucount (BD) and samples were processed according to the manufacturer’s instruction.
Staining of antigen-specific B cells
To identify RBD-specific B cells, recombinant purified RBD (DAGC149, Creative Diagnostics, New York, USA) was labeled with either AF647 or AF488. Double positive cells were considered as antigen-specific (Fig. 3). Antigens were labeled at the German Rheumatism Research Centre (DRFZ), Berlin with NHS esters conjugation for AF647 and AF488. A blocking experiment using unlabeled RBD in 100-fold concentration was used to ensure specificity of the staining (Fig. 3A). The number of recorded antigen-specific events ranged from 0-422 events. To ensure the specificity of our RBD-specific flow cytometric staining, we labeled memory B cells with fluorescently the two RBD and isolated them cytometrically. The isolated B cells were analyzed for their transcriptome and B cell receptor sequence using DropSeq (10X genomics). We were able to intercept and examine 168 cells from 8 vaccinated individuals 7 days after secondary immunization. This population of RBD-specific memory B cells was found to employ VDJ gene rearrangements using preferentially certain IgHV segments (IGHV3-30, IGHV3-53 and IGH3-23) and IGKV genes (IGKV1-39, IGKV1-33, IGKV1-9, and IGLV3-21) after mRNA inoculation, as described in Wang et al. (22). Most importantly, we even identified an RBD-specific clone (CDRH3: ARDYGGNANYFHY, CDRL3:QQYDNLPIT), which was found in 3 different vaccinees with highly identical amino acid sequence immunized as reported very recently upon Biontech or Moderna vaccinations (22).
Enzyme-linked immunosorbent assay (Euroimmun)
The Euroimmun anti-SARS-CoV-2 assay is a classical enzyme-linked immunosorbent assay (ELISA) for the detection of IgG to the S1 domain of the SARS-CoV-2 spike (S) protein, IgA to the S1 domain of the SARS-CoV-2 spike protein, and IgG to the SARS-CoV-2 NCP protein. The assay was performed according to the manufacturer´s instructions and as described previously (25, 26).
Surrogate SARS-CoV-2 neutralization test (GenScript)
This blocking ELISA qualitatively detects anti-SARS-CoV-2 antibodies suppressing the interaction between the receptor binding domain (RBD) of the viral spike glycoprotein (S) and the angiotensin-converting enzyme 2 (ACE2) protein on the surface of cells. The assay was performed according to the manufacturer´s instructions and as described previously (25, 26).
Single Cell RNA sequencing
Peripheral blood Cells were enriched from peripheral blood using StraightFrom Whole Blood CD19, CD3 and CD138 MicroBeads (Miltenyi Biotec) according to manufacturer’s instructions. Afterwards cell were stained, incubated with TotalSeq oligomer-conjugated hashtag antibodies ((TotalSeq-C anti-human Hashtag antibody 1 to 4) and sorted with a MA900 Multi-Application Cell Sorter (Sony Biotechnology).
Sorted populations were identified as plasmablasts (DAPI-CD3-CD14-CD16-CD38++CD27++), memory B cells (DAPI-CD3-CD14-CD16-CD38varCD27+) and activated T cells (DAPI-CD3+CD14-CD16-CD38+HLA-DR+). The three sorted populations were pooled in equal proportions and further processed for single cell RNA sequencing. Single Cell RNA-library preparation and sequencing, single-cell transcriptome sequencing as well as well as data analysis and statistics has been performed as previously described (51). All details can additionally be found in the supplementary materials.
Data Analysis and Statistics
All details can be found in the supplementary materials.
Acknowledgments: The authors are grateful to Dr. Michael Moesenthin, Dr. Peter Bartsch (both Dialysezentrum Burg), Dr. Ralf Kühn, Dr. Dennis Heutling (both Dialyse Tangermünde), Dr. Petra Pfand-Neumann (Nierenzentrum Köthen) and Dr. Jörg-Detlev Lippert (MVZ Diaverum, Neubrandenburg) for patient recruitment as well as Dr. Petra Glander and Pia Hambach for biobanking of samples. Funding: ES was funded by the Federal Ministry of Education and Research (BMBF) grant BCOVIT, 01KI20161. ES received a grant by the Berlin Institute of Health with the Charité Clinician Scientist Program funded by the Charité –Universitätsmedizin Berlin and the Berlin Institute of Health. MFM received a Starting Grant-Multi-Omics Characterization of SARS-CoV-2 infection, Project 6 ”Identifying immunological targets in Covid-19” from the Berlin Institute of Health. HS is receives funding by the Ministry for Science, Research and Arts of Baden-Württemberg, Germany. ALS is funded by a scholarship of the German Society of Rheumatology. AS and KK receive funding by the Sonnenfeldstiftung Berlin, Germany. TD is grantholder oft the Deutsche Forschungsgemeinschaft grants KO 2270/7 1, KO-2270/4-1 (KK); Do491/7-5, 10-2, 11-1, Transregio 130 TP24. MFM receives funding of the State of Berlin and the “European Regional Development Fund” with the grant ERDF 2014–2020, EFRE 1.8/11. AR is funded though the Deutsche Forschungsgemeinschaft (DFG) through the TRR130-P16 and TRR241 B03 grants. MFM is part of the Leibniz Association (Leibniz Collaborative Excellence, TargArt). HRA holds a scholarship of the COLCIENCIAS scholarship No. 727, 2015. AS and KK receive funding by a grant of the Chiesi GmbH. Author contributions: HRA, ES, ACL, ALS and TD developed the concept of the study. KB, FH, MC, UW, AS and ES collected patient’s samples. FSZ, ALS, HRA, HS, BJ, KL, GMG, MFG, MFM, AP, YC obtained the data. HR, ES, ALS, MFG, MFM and ACL, PD, FH analyzed the data. TD, ES, AS ALS and HR developed the theoretical framework. ACL, KK, KUE, GB, KB, AR and TD supervised the work. All authors developed, read, and approved the current manuscript. Competing interests: Authors declare that they have no competing interests. Data and materials availability: All data are available in the main text or the supplementary materials. Data from transcriptome sequencing and immune profiling in GEO under the accession GSE176442. This work is licensed under a Creative Commons Attribution 4.0 International (CC BY 4.0) license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. This license does not apply to figures/photos/artwork or other content included in the article that is credited to a third party; obtain authorization from the rights holder before using such material.
Focusing on your immunity is not difficult if you go for the right products. If you are looking for herbal immunity boosters, you must be aware of the medicinal properties of tulsi or holy basil leaves. Tulsi is known to be great for respiratory health and can make your immune system stronger easily. If you do not have a tulsi plant at home, you will have to go for herbal tulsi supplements that will be good for your health. You can even try having tulsi powder regularly by mixing it with water to boost your immune system easily.
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Studies have proved that proper immunity within the human body can prevent an attack by the Covid-19 virus. Since the outbreak of the pandemic, people all over the world have been in a mad rush to increase the body’s immunity. People have started consuming various types of medicines, different categories of food and fruits with the aim to strengthen the immune system. But you know what… you can increase your immune system by avoiding a few types of food material. Here’s a look at what you should avoid.
Sugar– Avoiding sugar can help you from turning into a diabetic. Foods with sugar as an ingredient must be avoided at all cost as it may decrease the immunity of the body and lead to other complications.
Salt – Consumption of excessive salt is again bad for the health. Various types of junk food like chips, bakery products and frozen food are high in salt content. According to the World Health Organisation (WHO), a person at the most can consume five grams of salt per day. If it exceeds the limit, the immunity of the body will suffer.
Fried food – It may look delicious and spicy, but high level of consumption can lead to health problems. Fried food can increase the risk of heart diseases and even heart attacks. Hence, avoid eating samosas, chips or deep fried ingredients.
Caffeine – Intake of too much caffeine can also affect your immunity. Drinking too much of tea or coffee can disturb your sleep patterns, which can result in an inflammatory response and compromise your immunity.