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Dorset Secret Travel Tip – Smugglers Inn, Osmington and Ringstead Bay

Smuggling is a fascinating part of Dorset’s history and the county’s World Heritage coastline is littered with smugglers coves. This travel tip article is about an exhilarating, yet undemanding coastal path walk. It starts in one such cove, hidden amongst some of England’s most magnificent coastal scenery. It then takes you to a pretty beach in a tranquil bay, before returning to a real smugglers inn which is one of the most picturesque traditional English pubs you’ll find anywhere.The walk starts at the pub which is unsurprisingly named, “The Smugglers Inn”. You will find it by driving westwards, along the A353, towards Weymouth. About six miles before Weymouth, and after passing a left hand turning, signposted Ringstead Bay, take the next left which is signposted Osmington Mills. There is also a helpful secondary signpost labeled “Smugglers Inn”. Continue along the lane as it meanders fairly steeply downhill for about three quarters of a mile. You will see the Smugglers Inn at the foot of the hillside on your left and the car park on higher ground to the right. You park here. At the time of writing it is a free car park but please understand that it is intended for pub patrons, so remember to have a drink or meal in the inn when you return later.Walk down the steps from the car park to the inn and look for a narrow path that leads along the left side of the building and goes to the rear where it becomes the start of the walk. When the walk opens up into a hilly field, head for the lower of the two styles and follow the footpath down to the cove. Here there is a very rocky and pebbly beach with a small waterfall that is fun to cross and makes an excellent backdrop for photographs.After spending some time exploring the smugglers cove, go back to the field and head for the other style, signposted Coastal Path and Ringstead. This path takes you to the cliff top and provides some superb views across the bay towards Portland and Weymouth Harbor. Look out for the wreck of a small ship that pokes through the surface at low tide but can also be seen under the waves at other times in the crystal clear, turquoise shallows at the foot of the cliff. Continue along the footpath until it descends to nearly sea level with a turn off right to the beach. This will bring you out onto the shingle and pebble, west end of Ringstead Bay. At this end you will find some interesting rock pools and an offshore reef that is uncovered by the tide.The bay stretches for about half a mile to where it ends at White Nothe, a dramatic, white cliff headland. It’s worth the walk to the far end of the beach because the further you go the less pebbly the beach gets and there is quite a bit of sand to be found once the tide goes out. About midway along the bay there are a few holiday homes, some permanent residences, a shop and a café about fifty yards inland and up a path from the beach. Swimming is safe for adults and children in the usually tranquil waters of the bay and there is plenty of grass above the beach for the kids to run around on. The beach is a great place to look for fossils, being part of the World Heritage site, aptly nicknamed, “The Jurassic Coast”. Unfortunately and despite its relatively isolated location, it is not used by naturists.When you have had enough time sunbathing, exploring the beach or swimming in the turquoise sea, return the same way as you came, remembering to stop off at the Smugglers Inn for drinks or a bite to eat. The locals call the inn, “Smugs” and it dates back to the 13th century. Its situation in the ravine between sheer cliffs has always made it a perfect retreat and landing spot for smugglers. When you go inside to order your drinks or food, you will find plenty of information to read up on about the famous smugglers who once frequented the place. Watch your head under the low roof beams and try to imagine the atmosphere in the days that a gang of notorious smugglers huddled around the huge fireplaces and secret alcoves, plotting their next run across the channel.As you sit back to enjoy a meal, you might pick up one of the many tourist leaflets that provide further travel tips and information about the Dorset coast and countryside. There is so much to see and do in this area. For naturists, Studland Bay, the UK’s most popular naturist beach lies only half an hour away.The weather is usually the fairest you will find in the U.K. but if you do strike it unlucky or don’t want to go to the beach, Dorset also offers plenty of indoor attractions too.

Real Estate Investing and Picking a Mentor

Ok, so I bet you have seen them time and time again, those late night infomercials, and everyone seems to know the big secret in real estate investing. Well the bad thing about these “gurus” is all they want to do is send you a course, filled with DVDs, CDs, books, or e-Books or whatever. I have personally bought a couple of these courses, and while they are filled with some helpful information. I have yet to step foot into the real estate investing business. I am not confident enough with what little knowledge I have acquired from the courses I have bought.I have spent well over $2000.00 on investing course, books, CDs, and DVDs, to no avail. What I have figured out, is that when you are choosing a real estate investing coach or mentor to find out how real estate invest works, you have to find someone willing to do it one on one. Someone that will take you by the hand, out in the field and show you first hand how it’s done.Don’t spend money on e-Books, 90% of them are filled with website links that lead to yet another product by the supposed guru, and he is wanting you to purchase this other course that is guaranteed to give you the real secret, and it only costs a couple thousand dollars. Well we are in the middle of a recession, so who can afford that. I am looking to make money not spend it. Now, don’t get me wrong, I am willing to spend the money, as long as I am going to learn things, and I feel that if I were to be taken and shown first hand how to evaluate, make an offer, get the deal, fix the property and sale it, I would be more than willing to spend another couple thousand dollars or so.But frankly I am done with the books, DVDs and CDs. I have enough in closet gathering dust that I couldn’t fit anymore in there. So when you are looking for the real deal, on how real estate investing works, you need someone that is going to take you out and show you how it’s done, just remember you are going to have to pay, good money, for such a service, but just think about the reward and the amount of knowledge you would gain from it.

US Insurance Companies and Life Insurance Quotes

The US is one of those countries in the world which boast a major number of life insurance companies. The various companies offer different life insurance quotes to its customers. One must know which policy he needs to cover all his expenses and then go for it.US Insurance Companies and Its PoliciesThe popularity of US life insurance policies have grown radically over the past few years. It observed 12% annual growth from the year 2002 to 2004, whereas only 3% growth in its assets was observed by the industry between the year 2000 and 2002.Some of the popular US insurance companies include MetLife, New York Insurance, Prudential Financial, Mass. Mutual Life Insurance, TIAA-CREF, UnumProvident, Principal Financial, Northwestern Mutual, Assurant, AFLAC, Lincoln National, Pacific Life, Thrivent Financial for Lutherans, Jefferson-Pilot, Conseco, Western & Southern Financial, Mutual of Omaha Insurance, Torchmark and Unitrin. These companies offer great insurance quotes to its customers.Out of these, Aviva plc is the fifth-largest insurance group in the world and second-largest insurance group in Canada. AXA is a French insurance group of companies engaged in life, health and other insurances. It ranks as the 15th biggest company in the world. Allianz is one of the largest financial services providers in the world, whose core business focuses around insurance. Besides, there is New York Insurance Company (NYLIC), which is the largest mutual life-insurance company in the United States. It is also considered as the largest life insurers in the world. All these insurance companies and many others as well offer various insurance quotes, which not only cover the insurer’s life, but also provide security against any loss of income and such accidents.About Life Insurance QuotesThere are various insurance quotes, but before purchasing a quote an insurer should make a thorough research about them in the market. These quotes depend upon the health issues, family history and other factors of an individual. There are some specialized insurance quotes available for those who have high cholesterol, height/weight issues, past experience of heart disease or Cancer. Besides these there are other factors which an insurer should verify before purchasing a policy. The five mistakes that often people make while purchasing a life insurance quote are:1. Apply for unconditional lowest term life insurance quote without taking into account other benefits.
2. Apply for a lower sum of coverage without considering the future expenses like college tuition fees, mortgage payments an others.
3. Assume that the life insurance is the best available without knowing that every company finances a little differently.
4. Not review old insurance policies and enquire whether the rates and products have changed.
5. Laps or cancel any insurance without finding out the worth of the policy in the Life Settlement market.Besides these points, one must know that most of the life insurance policies are purchased through an agent or broker, who might not always be reliable. Therefore, one can take help from his friends and relatives who can refer him to a trustworthy agent or broker.These are the most common pitfalls one must avoid to get the best life insurance quotes and make the best use of their insurance policies.

The Best Corner Home Office Desks – Styles You Simply Must Have

Decorating a home office is no small undertaking, especially if you want to make a professional looking environment for your home business. No matter what kind of business it is you run from home, you want to put your best foot forward and this means kitting out your office space with great furniture. Whether its several expensive pieces or one large item that serves a number of purposes, you need to furnish your office to reflect the kind of professional that you are.Buying office furniture can be pricey, and you might need a few items to kit out your domestic office with even the most basic set of furnishings. So how can you maximize your storage and desk space in a small office? Read on for the ultimate tips for finding furniture to suit your needs, without having to spend a fortune.Why corner home offices are the best choice: Interior decorators agree, a corner home office desk is the number one way to make the best use of your office space. Not only do you maximize your use of the available space, but you make a pretty stylish statement too.Corner home office desks come equipped with cabinets for your electronics, shelves for your books and of course a spacious work space. Because you make full use of the corner, you also have more legroom than you would have in any other space. There’s no doubt about it, a corner office desk is the best way to maximize the space in a small home office as well as creating a dramatic effect in a larger office.Corner home office desks are one of the best ways to meet all your furniture requirements in one go. It’s the most practical solution to all your storage needs, while providing a fantastic desk at the same time.Corner desks come in all shapes and sizes, from the simplest triangular desks that are only large enough for a computer or laptop, to large corner desks that meet all your needs with shelving and cabinets as well.Shopping for corner home office desks: If you are looking for a corner office desk, you are going to need to take a few measurements before beginning your shopping. Check what kind of space you have available, and measure the height and depth of the area you want to put your desk into. Also measure your current desk so you have an idea of a comfortable height for yourself.In any domestic office, your desk is the most important item of furniture, and well worth investing a bit of cash into. Don’t be surprised to see the cost of the higher end models when browsing; you need to keep in mind all the other items of furniture it is replacing.Looking around at the available selection, you will find many simpler corner desk models for smaller spaces as well. If your budget or available space is exceptionally small, then these might be the best choice for you. If you can afford to splurge, do treat yourself to a more deluxe model, you will appreciate the extra size and storage space greatly!A corner home office desk is a fantastic choice for any home professional that needs to create a welcoming and professional looking domestic office. Take care of your home office furniture needs could be as simple as buying the right desk

Selecting Your Home Office Desk

Success comes right after perfection. If you are perfect at whatever you do then success will follow you. If you have all the right equipment, you will be able to reach your destination and succeed at whatever you do. People working from home know how important it is to have the right tool at the right time. Only perfection brings any chance of success. So you must try to be purchase the best and perfect office desk and all of the furniture for your home office. Home office desks are one of the most important requirements of an office whether it is at home or at a company premises. Thus it is very important to pick the best desk for the office in your home from local stores or through online furniture stores. Here in this article you will find the methods for selecting a proper home office desk for your personal workspace.
Before you go out looking for your home office furniture you must first list the things you actually need and set a budget so that you do not make any compulsive purchases. Your list of things should also include tasks that you feel you will be accomplishing at your workstation. The list must also include the items that will be used or placed on the desks. You may also need filing cabinets for your desk so that you can keep your important documents accessible but also stored safely away. You may have frequent visitors at your home. In such cases you will want your home office desk to be aesthetically pleasing and appealing as well.
Secondly you must carefully measure your home office space so that you can anticipate your requirements. For a small area you may need a compact design whereas for a large home office space you may need a large office desk.
It is very important to be comfortable while you are working because only then you can work properly and efficiently. The home office desk and a comfortable office chair must provide optimum comfort to you. A proper office desk helps a lot in increasing your overall work efficiency. It’s better to look and select the desk that fulfills all of your requirements.
Online search can help you look for the best quality office furniture. This new technology can help you in selecting and purchasing office furniture for your home while sitting comfortably at one place. You can see and compare home office desks online and select furniture that is affordable to you and your budget. You can get an idea of what type of furniture you want and in what price range you would prefer. The information you gather online will help you in shopping for a home office desk and other furniture.
You must shop at your local office furniture store personally so that you can check if there are any damages or problems with the furniture you are selecting. You can also compare the prices you found during your online survey while visiting your local furniture store.
If you have a budget you must opt for ergonomic furniture because this furniture type is not only comfortable they are also durable and easy to handle. They also are the best remedy for your back pain, and other health related problems. They will help you feel relaxed while working overtime at the ergonomic desk and chair.

Home Office Desk Options: Choosing the Best for Your Needs

Your home office desk is important. Not only because you have an office at home and you need one, but mainly because of the way it meets your personal needs, both ergonomically and with regard to the storage facilities a good desk provides.An example of that is a desk that provides filing capacity in a deep drawer, which is an essential if your office has no room for a filing cabinet. For many people, their home office is no more than a cupboard or a similar small area. For others it could be larger than most people’s bedrooms. Irrespective of the space available to you, you will want a desk that perfectly meets your needs with regard to accessibility, storage and comfort – and don’t forget looks.Home Office Desk DesignWhether or not the design and look of your desk is important will depend upon the type of office you have. If you run a professional business from home, and may occasionally have the need for clients or suppliers to visit your office, then you will likely want something more than a laminated board with some drawers. There are many types of executive desk available online suitable for the most professional of home offices.Desks crafted from solid oak or with cherry or walnut veneers tend to be heavy, but they look very elegant and professional. You might prefer a more modern look, where metal and glass offer a more hi-tech finish than most wooden desks can achieve. You should combine your personal preferences with the expectations of visiting clients, and choose a home office desk to meet both needs.Desk Size: Naturally, the size of your office desk will depend on the available space. If that is not an issue you should select a desk with sufficient space for your computer – most are laptops these days and take up a lot less space than they once did. If you do not have enough room for a separate printer table, then your desk will also have to accommodate that, plus a router and also don’t forget your personal working space!Shape: A rectangular desk will make best use of restricted space than a round or oval desk. If you have little room, L-shaped desks make great use of space. Another popular design is a wall unit designed with bookshelves and storage space, with a desk projecting at right-angles to it. Many prefer this type of design, because their office storage and desk can be arranged as a corner unit, making maximum use of small office space.Storage: If you choose a 3-in-1 printer, incorporating a copier and scanner, your storage will be limited to printer paper, documents, files and books. As suggested earlier, one deep drawer can be fitted with filing rails, with another 3-4 drawers for less bulky items. If you use fax, that capability can transferred to your computer which can receive and send faxes to and from regular types of fax machine. You should also consider whether locks are necessary or not.Functional or Furniture?Is your home office desk fundamentally a piece of furniture or should its functionality be your main priority? Again, this may come down to whether you are running a genuine company or if the desk is simply for home use. There is no need for a functional item not to take the form of a beautiful piece of home furniture. In fact, many professional business desks would look perfectly at home in both a business and domestic environment.However, desks hand-made from solid oak, cherry or mahogany tend to be expensive, and more suited to the type of corporate finance that most individuals would find beyond them. The occasional domestic user would be reluctant to spend too much hard-earned income on a home office desk, and there are many good-looking desks available at economical prices that would look superb in a home office.To summarize… … your choice of desk will depend to a large extent on the use to which it will be put and on its location. The individual furnishing a small spare room as a home office will have different priorities to the professional home businessman or woman. In one case, the company may be financing the home office furniture, while in the other the cost will be coming from the home budget.Whichever is your reason for seeking a home office desk you will find a large selection of alternatives online. It makes sense to look online before visiting mall showrooms, because you can get a better idea of what is available on the market by visiting a number of different online furniture stores. The usual advice is to check it out online but purchase it offline once you see what you are buying. Then you will get no shocks on delivery!

How To Tow A Vehicle In Emergency

Call a professional towing service if you need to tow your vehicle.
Flatbed equipment
The operator loads your vehicle on the back of a truck.
This is the best way to transport your vehicle.
Wheel lift equipment
The tow truck uses two pivoting arms that go under the front tires and lift them off Ground. The rear tires remain on the ground. This is an acceptable way to tow your vehicle.

Trying to lift or tow your vehicle by the bumpers will cause serious damage. The bumpers are not designed to support the vehicle’s weight. Never tow your vehicle with just a rope or chain. It is very dangerous, since ropes or chains may shift from side to side or break. Improper towing such as towing behind a motorhome or other motor vehicle can damage the Transmission. If your vehicle must be towed with the front wheels on the ground:

1. Check the ground underneath the vehicle around where the transmission housing is For a fluid leak. If you find a leak, call a professional towing service and have your vehicle inspected by a dealer.

2. Put cloth on the edge of the cover. Carefully pry with a small flat-tip screwdriver or a metal fingernail file to remove the cover. The detachable towing hook mounts on The anchor in the front bumper.

3. Take the towing hook and the wheel nut wrench out of the luggage area.

4. Screw the towing hook into the hole, and tighten it with the wheel nut wrench Securely.

5. Hook the towing device to the towing hook.

6. Start the engine.

If it is difficult to turn on the engine, put the ignition switch in ACCESSORY or in ON position

7. Manual Transmission models: Shift to Neutral.

8. Continuously Variable Transmission models: Depress the brake pedal.

9. Shift to Drive mode and hold for five seconds, then to Neutral

10. All models: Release the parking brake.

If your vehicle must be towed with the front wheels on the ground:

Continuously Variable Transmission CVT Models only:

If you cannot shift the transmission or turn on the engine, will damage the transmission. Your vehicle must be transported with the front wheels off the ground.

Models with the keyless access system have an ENGINE START/STOP button instead of an ignition switch.


If you cannot turn on the engine, you may experience the following while your vehicle is being towed.

Braking may become difficult since the brake system’s power assist is disabled. Steering wheel becomes heavy as the power steering system is disabled.

Turning the ignition switch to LOCK (0*1 locks the steering wheel.

With the front wheels on the ground, it is best to tow the vehicle no farther than 80 km, and keep the speed below 55 km/h. Going down a long slope heats up the brakes.

This may prevent the brakes from working properly. If your vehicle needs to be towed on an incline, call a professional towing service.

Make sure to use the properly-designed and attached towing equipment. Manual transmission models Turning the ignition switch to LOCK (0*1 locks the steering wheel.

With the front wheels on the ground, it is best to tow the vehicle no farther than 80 km, and keep the speed below 55 km/h. Going down a long slope heats up the brakes.

This may prevent the brakes from working properly. If your vehicle needs to be towed on an incline, call a professional towing service.

Make sure to use the properly-designed and attached towing equipment.

Why You Should Study International Postgraduate Courses in Nursing

Nurses are a boon to the healthcare sector and the society overall as it is with their relentless efforts that efficient patient care is being possible. Also, considering the financial advantages of being a nurse, it is important to know that nursing as a profession is highly rewarding and respectable if you’re in the right place. With the continuous increase in demand for highly skilled nurses across the globe, a record number of students can get the opportunity to work in the healthcare sector as a nurse and serve the society. So, thinking on these lines, if you are an existing or an aspiring nurse in your country, you might want to enhance your career prospects on an international level by choosing to study postgraduate course in nursing in Canada.

Nursing in Canada has an endlessly wide scope as there is a huge unattended population of old people getting sick with multiple illnesses. It is for these people that nursing services are highly being demanded and in response to this demand, the government of Canada is accepting more than 2, 50,000 applications of healthcare workers who plan to move abroad in search of better employment opportunities. Making a move for higher international education may seem like a tough task initially but looking at the broader aspects of it, you can be assured that it would benefit you personally and professionally in a life-changing way. Needless to say, nursing life in Canada is far more respect worthy and esteemed as compared to that in developing nations.

When thinking of choosing a suitable province to study in Canada, one can look for postgraduate nursing courses in Ontario as the place itself is a hub of multiple employment opportunities. Ontario offers a friendly territory for all the new immigrants as it has a multi-cultural environment which brightens the scope of finding like-minded people around. However, before choosing to study the postgraduate nursing courses in Canada you must identify the specialty of your interest and then apply with a recognized designated learning institution. To make sure that the entire procedure from putting in an application to finally settling in Canada, it is important for you to choose a trusted education partner and at INSCOL, we make sure to be there from beginning till the end. To know more about exploring global opportunities as a nurse, choose to get in touch with INSCOL from our website and begin your international journey of experiences.

The Importance of Context in Covid-19 Vaccine Safety

Vaccine safety is critical for the successful implementation of any vaccination program, especially during a pandemic. In February 1976, the Centers for Disease Control and Prevention confirmed a cluster of cases of severe influenza-like illness among Army recruits at Fort Dix, New Jersey.1 A swine influenza A strain that resembled the 1918 pandemic influenza strain was identified,2 and a vaccination program was subsequently initiated for the entire U.S. population. After more than 40 million persons were vaccinated, a small excess risk of Guillain–Barré syndrome was noted, with an attributable risk of approximately 1 case per 100,000 doses administered. Given these concerns and because the pandemic did not materialize, the vaccination program was halted in December 1976 so that the issue could be explored further. This experience shed light on the need for real-time vaccine safety surveillance and the importance of context in decision making during a pandemic.

In a study now reported in the Journal by Barda et al., the investigators simultaneously evaluated the risk of adverse events among persons (≥16 years of age) who had received the BNT162b2 vaccine (Pfizer–BioNTech) and the risk of the same events after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection.3 The authors used data from the largest integrated payer–provider health care organization in Israel, in conjunction with data on SARS-CoV-2 polymerase-chain-reaction tests and data on coronavirus disease 2019 (Covid-19) vaccine administration from the Israeli Ministry of Health.

This use of multiple data sets highlights the importance of investment in digital capabilities and meaningful integration across systems in order to provide real-time answers to key public health questions. The design of rigorous postauthorization vaccine safety studies during the Covid-19 pandemic has been a challenge because the pandemic itself has caused changes in health care utilization, the rollout of Covid-19 vaccines has occurred in phases because of initial supply limitations, and there have been disparities in access to vaccines. Barda et al. broadly addressed many of these challenges by emulating a trial that matched eligible vaccinees to unvaccinated controls according to sociodemographic characteristics, the number of preexisting chronic health conditions, previous health care utilization, and pregnancy status.

In the vaccination analysis, the study included 42 days of follow-up (i.e., 21 days after the first dose and 21 days after the second dose). This analysis accounted for seasonal and secular trends by matching on the day of vaccination, rather than relying on historical risk estimates that may not have been comparable in the pandemic setting. In the SARS-CoV-2 analysis, a similar approach was used to match persons with a newly diagnosed infection to uninfected persons.

Although the risk estimates in the vaccination and the SARS-CoV-2 analyses were not directly comparable because of differences in the populations (i.e., events were evaluated per 100,000 vaccinated persons and per 100,000 infected persons, respectively), these risks were placed in context. The most salient example is myocarditis, which has received much attention recently given the preponderance of reported cases after vaccination among adolescents and young adults and the incidence of myocarditis observed after SARS-CoV-2 infection.4-6 In the population-based cohort in the study conducted by Barda and colleagues, the risk ratios for myocarditis were 3.24 (95% confidence interval [CI], 1.55 to 12.44) after vaccination and 18.28 (95% CI, 3.95 to 25.12) after SARS-CoV-2 infection, with risk differences of 2.7 events per 100,000 persons (95% CI, 1.0 to 4.6) and 11.0 events per 100,000 persons (95% CI, 5.6 to 15.8), respectively. What is even more compelling about these data is the substantial protective effect of vaccines with respect to adverse events such as acute kidney injury, intracranial hemorrhage, and anemia, probably because infection was prevented. Furthermore, the persons with SARS-CoV-2 infection appeared to be at substantially higher risk for arrhythmia, myocardial infarction, deep-vein thrombosis, pulmonary embolism, pericarditis, intracerebral hemorrhage, and thrombocytopenia than those who received the BNT162b2 vaccine.

National discussions about benefit–risk balance often focus on the benefits of preventing symptomatic disease, hospitalization, or death due to Covid-19 and the risks of serious adverse events after vaccination.7,8 As specific adverse events such as myocarditis are highlighted, however, the lack of corresponding specificity about benefits can hamper efforts to communicate effectively with patients. Messenger RNA (mRNA) vaccines may be associated with myocarditis, but they can also prevent cases of myocarditis, acute kidney injury, arrhythmia, and thromboembolic disease. The key to comparing these risks depends on the risk of SARS-CoV-2 infection to an individual person, and that risk can vary according to place and over time. Given the current state of the global pandemic, however, the risk of exposure to SARS-CoV-2 appears to be inevitable.

One major limitation of this study is the lack of risk estimates according to age group and sex. For example, thrombosis with thrombocytopenia syndrome occurs predominantly in young adult women who have received adenoviral vector vaccines against SARS-CoV-2, whereas myocarditis predominantly occurs in male teens and young men who have received mRNA vaccines.5,9,10 Age- and sex-stratified comparisons that reflect local epidemiologic factors might support public understanding of different approaches to vaccine use in different countries, such as Israel, the United Kingdom, and the United States. Other limitations of the study include the paucity of data regarding younger teens and children, the conservative assumption that vaccines have no effect on transmission, and the absence of medical record review to validate computable phenotypes (i.e., algorithms used to identify a cohort on the basis of patient records).

As new knowledge of the safety and benefits of vaccines continues to evolve, studies like this one may help to support decision making about the use of Covid-19 vaccines. The benefit–risk balance should be reassessed, refined, and communicated as the disease burden changes, new variants and safety signals emerge, and vaccine effectiveness begins to wane. Context matters, which means that we as a country need to be ready for continual learning and change.

No Correlation between Anti-PF4 and Anti–SARS-CoV-2 Antibodies after ChAdOx1 nCoV-19 Vaccination

Vaccine-induced immune thrombotic thrombocytopenia (VITT), also known as thrombosis with thrombocytopenia syndrome, is a rare but potentially fatal complication of vector-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines.1-3 The clinical picture and the serologic findings in patients with VITT resemble heparin-induced thrombocytopenia.1-3 Several groups have reported the presence of platelet factor 4 (PF4)–reactive antibodies in patients with VITT.1-3 IgG from patients with VITT induces platelet activation and aggregation by cross-linking Fcγ receptor IIA on platelets.1 PF4 is a tetrameric protein that is released from platelet alpha granules on activation. VITT antibodies bind to the heparin-binding site on PF4.4 The link between vaccination and the formation of anti-PF4 antibodies is yet to be determined. A proposed mechanism includes cross-reactivity between anti–SARS-CoV-2 and anti-PF4 antibodies.5 In the current study, we investigated the correlation between anti–PF4–heparin antibodies and anti–SARS-CoV-2 antibodies in vaccinated health care workers (healthy controls) and in vaccinated patients with clinically suspected VITT.

The level of anti–PF4–heparin antibodies was measured with the use of an enzyme-linked immunosorbent assay (ELISA), and the levels of antibodies against various antigenic sites of the SARS-CoV-2 spike protein (spike trimer, receptor-binding domain [RBD], subunit 1 [S1] domain, and subunit 2 [S2] domain) and against nucleocapsid protein were measured with the use of a bead-based assay (Luminex). Antibodies were measured in 101 healthy controls 2 weeks after the first dose of ChAdOx1 nCoV-19 (Oxford–AstraZeneca) had been administered and in 59 patients with clinically suspected VITT between 11 and 22 days after the first dose had been administered. The ability of the sera to activate platelets was tested with the use of a modified heparin-induced platelet aggregation assay. Details of the methods are provided in the Supplementary Appendix, available with the full text of this letter at NEJM.org.

Figure 1.

Antibody Levels and Correlation Analysis.
VITT was confirmed in 20 of 59 patients (34%) on the basis of a positive PF4 ELISA and a positive modified heparin-induced platelet aggregation assay (Table S1 in the Supplementary Appendix). The level of anti–PF4–heparin antibodies was higher among the patients with confirmed VITT than among the healthy controls and the patients who did not have VITT (Figure 1A and Table S1). The 95% confidence intervals for the differences between the groups are presented in Table S2; these confidence intervals were not adjusted for multiplicity and therefore cannot be used to infer effects. The levels of antibodies against spike trimer, RBD, S1 domain, and nucleocapsid protein were similar in the three groups. The levels of antibodies against S2 domain were lower among the patients who did not have VITT than among the persons in the other two groups. We did not find any correlation between the level of anti–PF4–heparin antibodies and the level of anti–SARS-CoV-2 IgG antibodies in any of the three groups (Figure 1B and Table S3).

Moreover, the levels of anti–SARS-CoV-2 antibodies did not differ substantially between vaccinated persons without complications (i.e., the healthy controls) and patients with VITT. Similarly, Scully et al.2 reported that the levels of antibodies to spike protein and RBD in patients with VITT were in the same range as those of the recipients of one dose of ChAdOx1 nCoV-19. Furthermore, our study did not show a correlation between anti–PF4–heparin antibodies and anti–SARS-CoV-2 antibodies in patients with VITT. Although a preprint publication suggested that spike protein shares an immunogenic epitope with PF4, purified anti-PF4 and anti–PF4–heparin antibodies from patients with VITT did not show cross-reactivity to recombinant SARS-CoV-2 spike protein.5

Our results do not support the hypothesis that the immune response against SARS-CoV-2 proteins leads to the formation of anti-PF4 antibodies in patients with VITT. However, we cannot exclude the possibility of cross-reactivity between a subgroup of anti–SARS-CoV-2 antibodies and a subgroup of anti-PF4 antibodies. A better understanding of the link between vaccination and VITT is necessary for the development of more targeted therapies.