COVID-19 and PIDs FAQs

• To date (02-11-2021), global surveys aimed at collecting data on COVID-19 in PID patients do not point to an increased risk of COVID-19, especially not in its severe form, although some cases have been reported. Patients with PID have generally suffered a less severe course than expected, however the rate of severe disease in younger age groups, as well as rates of admission to ICU, are higher for patients with PID versus the general population.
• Certain PID patients might be at higher risk than others to be infected or develop a more severe course of disease and patients with PIDs should take extra care to avoid getting this infection. For more information about specific PIDs at higher risk: Read the Joint statement on COVID-19 (published 28.10.2021).
• Additionally, any respiratory virus that can be spread from person-to-person may be a risk for PID patients. Therefore, PID patients should be cautious and keep track of developments of COVID-19 in their region.
• Whilst immunoglobulin (Ig) replacement therapy provides protection against a wide range of infections, it does not guarantee immunity against COVID-19.

• To date (02-11-2021), global surveys aimed at collecting data on COVID-19 in PID patients do not point to an increased risk of COVID-19, especially not in its severe form, although some cases have been reported. Patients with PID have generally suffered a less severe course than expected, however, the rate of severe disease in younger age groups, as well as rates of admission to ICU, are higher for patients with PID versus the general population.
• However, certain PID patients might be at higher risk than others to catch this infection or a more severe course of the disease. In the absence of more precise data, patients with PID need to take extra care to prevent from getting this infection.
• In general terms, for PID patients with lung complications, it is possible that the risk for an infectious disease is higher and that you might be more severely affected if catching the SARS-CoV-2 virus.
• PID patients with overweight, old age, cardiovascular disease, diabetes mellitus and/or significant respiratory issues (severe asthma, bronchiectasis or chronic respiratory failure) should receive special attention (as for any risk of respiratory infection)
• Impaired Type I interferon (IFN) signaling is emerging as an important factor for control of SARS CoV-2, from large studies of infected patients. Both the presence of antibodies that neutralize type I IFN and genetic variation in the type I IFN pathway have been demonstrated to be associated with severe COVID-19. Thus, patients with forms of PID that result in reduced type I IFN signaling should be considered at high risk of severe COVID-19.
• Special attention should be given to patients with APS1/APECED (Autoimmune Polyendocrine Syndrome) due to mutations in AIRE. These individuals develop high titers of serum anti type1interferons, that have been found in patients and are associated with more severe forms of COVID-19.
• For more information about specific PIDs at higher risk: Read the Joint statement on COVID-19 (published 28.10.2021).
• Keep in mind that it is always essential to regularly continue to take the treatment for your PID. Plasma Derived Medicinal Products (PDMPs), such as immunoglobulins (IVIG or SCIG) are safe and will protect you from many other infections.
• Whilst immunoglobulin (Ig) replacement therapy provides protection against a wide range of infections, it does not guarantee immunity against COVID-19.
• PID patients should be cautious, follow recommendations, and keep track of developments of COVID-19 in their region.

* SARS-CoV-2 is the virus that causes the COVID-19 infection.

•  Ideally these patients would be tested, show negative results, and thus avoid isolation.

• COVID-19 is an infectious disease, but it does not behave exactly like a classic airborne infectious disease, as for example the swine flu in 2009.
• Some patients experience severe symptoms that require hospitalization (sometimes in intensive care units), caused by an abnormal immune response called hyperinflammation.
• The immune systems response to the virus is unbalanced, which can lead to the severe symptoms of respiratory distress, subcutaneous skin symptoms, rheumatological symptoms features among others.
• Due to the hyperinflammation it is believed that immunotherapy is a major component of the therapeutic arsenal for treating severe cases of COVID-19.

• To date (02-11-2021), global surveys aimed at collecting data on COVID-19 in PID patients do not point to any specific PID subgroup being more at risk for catching a COVID-19 infection.
• However, certain PID patients may still be at higher risk than others to experience a more severe course of the disease and PID experts will take this into consideration when treating their patients.
• PID patients with overweight, old age, cardiovascular disease, diabetes mellitus and/or significant respiratory issues (severe asthma, bronchiectasis or chronic respiratory failure) should receive special attention (as for any risk of respiratory infection).
• Impaired Type I interferon (IFN) signaling is emerging as an important factor for control of SARS CoV-2, from large studies of infected patients. Both the presence of antibodies that neutralize type I IFN and genetic variation in the type I IFN pathway have been demonstrated to be associated with severe COVID-19. Thus, patients with forms of PID that result in reduced typeI IFN signaling should be considered at high risk of severe COVID-19.
• Special attention should be given to patients with APS1/APECED (Autoimmune Polyendocrine Syndrome) due to mutations in AIRE. These individuals develop high titers of serum antitype1interferons, that have been found in patients and associated with more severe forms ofCOVID-19.
• For more information about specific PIDs at higher risk: Read the Joint statement on COVID-19 (published 28.10.2021).

• Human coronaviruses commonly cause mild to moderate illness in the general population. So far, the main clinical signs and symptoms reported in this outbreak vary from no symptoms at all to fever, tiredness, fatigue, dry cough and running nose.
• Some patients also experience aches and pains, nasal congestion, sore throat, diarrhea and skin rash. These symptoms are usually mild and begin gradually.
• In children and pre-teens, a form of vasculitis close to the already known Kawasaki disease has been recently described (see next question).
• Some people become infected but don’t develop any symptoms and don’t feel unwell. Approximately 80% of the affected people recover from the disease without needing special treatment. According to the World Health Organization about 15% become seriously ill and require oxygen, with 5% becoming critically ill and needing intensive care.
• Word of caution: Some COVID-19 patients might experience shortage of breath and require oxygen administration at the hospital. It has been reported that evolution to a more severe form requiring urgent medical care can be very rapid (within a few hours).

• Although most people recover well from a SARS-CoV-2 infection, some individuals experience a range of post-COVID symptoms that can last weeks or months after first being infected. Long term COVID can happen to anyone who has had COVID-19, even if the illness was mild, or if they experience no symptoms at all.
• People with long COVID-19 report different combinations of the following symptoms: tiredness or fatigue, difficulty concentrating or thinking, headache, loss of smell or taste, dizziness, heart palpitations, cough etc.8 More research is needed to identify how common these long-term effects are, and how these symptoms will evolve over time.

• It has become clear since the start of the pandemic that in rare cases some children suffer from a post-inflammatory syndrome known as multisystem inflammatory syndrome in children (MIS-C), sometimes requiring intensive care approximately 2-4 weeks after primary COVID-19 infection.
• Patients with MIS-C usually have a history of recent SARS-CoV-2 infection, epidemiologic link, and/or antibody responses demonstrating prior infection. These children frequently had asymptomatic or mildly symptomatic primary infection.
• MIS-C has been observed in children around the world, and rates have been observed to increase following COVID-19 surges. The presenting symptoms frequently include fever, abdominal pain, conjunctivitis (redness of the eyes), rash, irritability, headache and in severe cases shock and cardiac involvement.
• Treatment is supportive and may include anti-inflammatory agents such as IVIG and steroids, and other medications to reduce the risk of clotting. The syndrome has features similar to Kawasaki disease (KD), but also features of toxic shock syndrome (TSS).
• Although the number of cases is more limited, similar symptoms have also presented in adult patients. The precise triggers of the exaggerated inflammatory response after COVID-19 have not been identified, and there is no evidence that therapy for acute COVID-19 prevents or increases the risk for MIS-C.

• The transmission mode of SARS-CoV-2 is similar to the previous coronavirus outbreaks, spreading from person to person through:
  – Liquid particles spreading when coughing, sneezing, speaking, singing or breathing heavily. These particles can vary in size from larger respiratory droplets to smaller aerosols.
  – Close personal contact with an infected person (shaking hands or touching)
  – Touching contaminated surfaces and then touching eyes, nose or mouth with unwashed hands
• SARS-CoV-2 RNA (Ribonuclease acid) has been detected in faeces, blood, serum, saliva, nasopharyngeal specimens, urine, ocular fluid, breast milk and in placental or fetal membrane samples.
• Findings have also demonstrated that children may release virus in the stools up to 15 days after recovering from COVID-19. This means that keeping distance, cough etiquette and frequent hand washing should be applied even after clinical recovery.
• The incubation period for COVID-19 is currently estimated to range from 1-14 days, with a median incubation period of five to six days. The virus has been identified in patients a few days before demonstrating symptoms (pre-symptomatic), peaking in the second week after infection (3-6 days after onset of symptoms).
• A small number of cases of animals testing positive to COVID-19 after contact with infected humans have been reported. It is recommended that people who are sick with COVID-19 and people who are at risk limit contact with animals. When handling and caring for animals, basic hygiene measures should always be implemented.

• There are currently multiple mutations circulating globally, in addition to those originating from the United Kingdom, Brazil, South Africa etc. It is also likely that there are multiple mutations within these countries as well.
• It is important to remember that a virus almost always mutates and that some mutations may affect the virus negatively (i.e. these mutations can vanish without being detected).
• Some mutations confer a selective advantage to the virus. This may lead to a prominent representation of new mutations in the pool of viruses that circulate. Some of these mutations confirm selective advantages to the virus in terms of transmission (they are more contagious). This does not necessarily mean the mutation will lead to a more severe course of the disease, but it is possible that some variations might in the future.

• The virus does not only transmit from person to person through respiratory droplets spread for example when coughing or sneezing. As an example, the virus can also transmit if an infected person coughs while covering their mouth with their hand and then touches someone else who in turn touches their eyes, nose or mouth with unwashed hands.
• There have been some reports of people who have tested positive for SARS-CoV-2 with only minor or no symptoms at all. In these cases, the infected person has still been able to transmit the virus to people who then become symptomatic, with minor or sometimes more concerning symptoms.
• Incubation period can vary between 1-14 days in the general population, but it may be longer for PID patients.
• The fewer people who are exposed to an infected person the better. This is why quarantine for 2 weeks is usually recommended for people infected with SARS-CoV-2.

• The data regarding the contagiosity is still scarce.
• However, there have been some reports of people who have tested positive for SARS-CoV-2, showing only minor or no symptoms at all. In these cases, the infected person has still been able to transmit the virus to people who then become symptomatic, with minor or sometimes more concerning symptoms.

•  Serology tests are blood-based tests that can be used to identify whether people have been exposed to a pathogen by looking at their immune response. The serology tests look for the presence of antibodies. The antibodies detected by this test indicate if a person has had an immune response to SARS-CoV-2 (with symptoms or asymptomatic).
• In contrast, the RT-PCR tests can only indicate if a person is currently infected with the virus and not if a person has been infected and recovered.
• There are currently various serology tests available online for people to do in their homes, but these tests need to be validated as they may not be reliable. We recommend only using validated home tests.
• When validating a serology test the sensitivity and specificity are key indicators. This is to ensure that the test is sensitive enough to detect all patients who have had the COVID- 19 infection and that it is specific enough to only detect patients who has had the COVID- 19 infection.
• Serology test rarely tests 100% for both sensitivity and specificity and it is likely that there will still be some false negatives and false positives. Due to this they need to go through numerous steps to ensure that they are validated for the market.
• Please note that if you have tested positive with a serology test and already recovered, it may not mean that you are immune or noninfectious. We encourage PID patients to continue being cautious.

• For patients with PID who are not able to produce antibodies (such as patients with agammaglobulinemia or other defects of antibody production), serology tests will not be useful.
• For other forms of PID (including those treated with Ig replacement therapy), this test may also not be of help to assess the patient’s response, as immunoglobulin preparations, depending on the date of collection, now contain anti-SARS-CoV-2 IgG.

This can be detected using a PCR test (usually not the ones performed using a regular nasal swab) but instead it is necessary to sequence the full RNA (i.e. the genomic material of the virus) to precisely identify which variant the person is infected with.

• Any respiratory virus that can be spread from person-to-person may be a risk for PID patients. Therefore, PID patients should be cautious and keep track of developments of COVID-19 in their region.
• Whilst immunoglobulin (Ig) replacement therapy provides protection against a wide range of infections, it does not guarantee immunity against coronavirus.
• The World Health Organization’s (WHO) and the Centers for Disease Control and Prevention’s (CDC) recommendations to reduce exposure to and transmission of COVID-19 include, but are not limited to, the list below.
• The MOST IMPORTANT means to prevent infection are:
  – Wash hands frequently (every hour) with soap and water for 20 seconds, (if not possible use alcohol-based hand rub), especially after direct contact with ill people or their environment
  – Avoid touching eyes, nose and mouth
  – Avoid close contact (at least 1 meter/3 feet) with people suffering from acute respiratory infection
  – Avoid close contact (at least 1 meter/3 feet) with anyone who has fever and cough
  – For extra precaution, avoid close contact (at least 1 meter/3 feet) with all other people when going outside your home
  – Avoid greeting people by shaking hands, kissing or hugging
  – Respect the confinement measures wherever these are applicable
• People with symptoms of acute respiratory infection need to practice cough etiquette (maintain distance, cover coughs and sneezes with disposable tissues or clothing, and wash hands) and wear a respiratory mask if instructed by their local health care provider. It is strongly recommended for people with symptoms to get tested.
• If you feel unwell and experience symptoms such as fever, cough and/or difficulty breathing, seek prompt medical assistance from your health care provider.

• Masks can be effective if the person wearing it has the appropriate training for a good fitting mask, but if not used appropriately they can pose a risk for contamination. The mask needs to be replaced regularly. Guidance from the World Health Organization on the appropriate way of wearing masks includes:
  – Before putting on a mask, wash your hands (with alcohol-based hand rub or soap and water).
  – Cover mouth and nose with mask and make sure there are no gaps between your face and the mask.
  – Avoid touching the mask while using it; if you do, clean your hands with alcohol based hand rub or soap and water.
  – Replace the mask with a new one as soon as it is damp and do not re-use single-use masks.
  – To remove the mask: remove it from behind (do not touch the front of mask)
  – Discard immediately in a closed bin; clean hands with alcohol-based hand rub or soap and water.
•  Many countries have taken measures for citizens to wear masks when spending time outside their homes and we advise to follow national guidelines. If you have symptoms you should wear a mask to protect people in your surroundings. If you are not able to wear a facemask (for example, because it causes trouble breathing), then you should do your best to cover your coughs and sneezes, and people who are caring for you should wear a facemask if they enter your room. If a shortage occurs, masks should be reserved for hospital staff and people experiencing symptoms.

• To date (02-11-2021), global surveys aimed at collecting data on COVID-19 in PID patients do not point to an increased risk of COVID-19, especially not in its severe form, although a few cases have been reported.
• However, certain PID patients might be at higher risk than others to catch this infection or a more severe course of the disease. In the absence of more precise data, patients with PID need to take extra care to prevent from getting this infection.
• Even after full vaccination, people should remain vigilant and continue to follow hygiene guidelines (masks, handwashing etc.) until herd immunity is reached.
• PID patients with overweight, old age, cardiovascular disease, diabetes mellitus and/or significant respiratory issues (severe asthma, bronchiectasis or chronic respiratory failure) should receive special attention (as for any risk of respiratory infection).
• Impaired Type I interferon (IFN) signaling is emerging as an important factor for control of SARS CoV-2, from large studies of infected patients. Both the presence of antibodies that neutralize type I IFN and genetic variation in the type I IFN pathway have been demonstrated to be associated with severe COVID-19. Thus, patients with forms of PID that result in reduced typeI IFN signaling should be considered at high risk of severe COVID-19.
• Special attention should be given to patients with APS1/APECED (Autoimmune Polyendocrine Syndrome) due to mutations in AIRE. These individuals develop high titers of serum antitype1interferons, that have been found in patients and associated with more severe forms ofCOVID-19.
• For more information about specific PIDs at higher risk: Read the Joint statement on COVID-19 (published 28.10.2021).
• Immunosuppressive drugs (in particular corticosteroids), might limit signs of infections (fever and other clinical symptoms). It is this recommended to contact your PID expert physician in case of unexplained change in clinical status including your well-being.
• Keep in mind that it is always essential to regularly continue to take the treatment for your PID. Plasma Derived Medicinal Products (PDMPs), such as immunoglobulins (IVIG or SCIG) are safe and will protect you from many other infections.
• For everyone, including PID patients, we strongly recommend you to keep aware of the latest information on the COVID-19 outbreak in your region, for example provided by the World Health Organization’s (WHO), the European Centre for Disease Prevention and Control (ECDC) and by your national and local public health authorities.

• Beyond the general precautions for all PID patients, the recommendations for your child will depend on the underlying PID. Thus, we recommend discussing it with your child’s PID expert.
• Keep in mind that it is always essential for your child to regularly continue to take the PID treatment. Plasma Derived Medicinal Products (PDMPs), such as immunoglobulins (IVIG or SCIG) are safe and will protect you from many other infections.
• If your child’s school has been suspended, we recommend following school guidance to ensure that your child can continue with their education.

• There is no evidence to date that more frequent dosing of Ig in general will offer more protection.
• For patients with lung disease or a history of serious infectious diseases, especially COVID-19, it may be an option to increase the IVIG dosage. However, this should be personalised and agreed between the patient and the PID expert, not seen as a general approach.
• There is no evidence to date that more frequent dosing of Ig in general will offer more protection.
• For PID patients whose condition does not require to be under regular Ig replacement therapy, there is no need to start Ig replacement therapy since no antibodies targeting COVID-19 is expected to be contained in the existing preparations.
• There is no recommendation to give immunoglobulins to the general population to protect
  or treat people against COVID-19.

• Hydroxychloroquine and chloroquine are drugs used to prevent and treat for example malaria, rheumatoid arthritis and lupus.
• It was, based on in vitro data and on shallow clinical data, believed to show efficacy but recent studies have shown that hydroxychloroquine and chloroquine may instead increase the mortality rate in COVID-19 patients.
• Reports from the WHO solidarity trial state that hydroxychloroquine had little or no effect on overall mortality, initiation of ventilation and duration of hospital stay in hospitalized patients.

• There is no proof that there is cross protection between influenza vaccine and COVID- 19.
• To avoid a co-infection with the influenza virus and COVID-19, it is recommended that all PID patients and their close contacts be vaccinated against seasonal flu. Please always refer to your PID expert to select the best flu vaccine for you. For most PID patients only inactivated flu vaccines will be indicated. For some specific cases live attenuated ones may also be an option.
• All PID patients should consult their PID expert physician about seasonal flu vaccine. Please note that recommendations will vary between PID patients and specialist advice should always be sought before receiving vaccinations
• Read more about PID and vaccination here.

• Antibiotic prophylaxis is not believed to help avoid COVID-19 infection.
• If you are already under a regular treatment, you should not stop it, but PID patients should not self-medicate. Please contact your PID expert for further advice.

• It is believed that vitamin D may play a role in regulating the cytokine inflammatory response that causes the acute respiratory distress syndrome, characterising the severe forms of COVID-19.
• Vitamin D cannot be considered a preventive or curative treatment for SARS-CoV-2 infection. However, by mitigating the inflammation and its consequences, it could be considered an addition to any form of therapy.

• If a country has started lifting the confinement measures it is because their authorities has made a thorough risk assessment, concluding that it is safe for people to leave their homes.
• In this case PID patients should generally follow their national guidelines but continue with recommended hygiene measures.
• For PID patients with higher risk for a severe course of the disease it may be considered to continue working from home, to not send the children back to school and to wear special masks (FFP2) for increased personal protection. However, many of these measures present a strong confinement to life and the cost and benefit needs to be balanced.
• It is important to understand that de-confinement measures do not mean that the virus has been extinguished. Confinement has been the strategy in many countries to “flatten the curve” of infections and to avoid overwhelming the health care systems. In many of these countries there is still only a small proportion of the population that has been exposed to the virus so far and de-confinement may lead to a further increase in infections. Hygiene measures and social distancing are still key to protect PID patients after de- confinement.

• This is a new virus and we are learning more and more each day. This pandemic includes various dimensions and until now many measures have been put in place as a response.
• Decisions on health care policy are taken on a national level and for this reason guidelines regarding confinement, masks, tests and so on may vary slightly in each country.
• For example, two countries with similar numbers of infected patients may have not have equally developed health care systems and therefore the measures may be different.
• For treatments there is a much more standardized approach and health care professionals and researchers are collaborating all over the world to enhance the knowledge and generate validated data on the best treatment for this virus.

• Visit WHO’s COVID-19 vaccine development landscape tracker for latest status on vaccines.
• There are several types of vaccines and all of them aim to prepare our immune systems to recognize and fight the SARS CoV-2 virus that causes COVID-19. Sometimes this process can cause side effects, but they are generally mild.
• All COVID-19 vaccines that are in development are being carefully evaluated in clinical trials and will be authorized or approved by European Medicines Agency (EMA) or FDA only if they are able to prevent COVID-19 in the majority of people and if they do not cause major side effects.
• For more information: Read the Joint statement on COVID-19, including information on vaccination for patients with PID. (published 28.10.2021).
• Please note that most PID patients (but not all) should not take live vaccines. All PID patients should consult their PID expert physician before receiving vaccinations.

• The COVID-19 vaccines that are currently in development or have been approved provide at least some protection against new virus variants because these vaccines elicit a broad immune response involving a range of antibodies and immune cells, according to the World Health Organization.

• Currently, there is not enough validated data to establish the mid-term to long-term efficacy and side effects for the approved COVID-19 vaccines in the population, including patients with PID. However, based on the very good tolerability and efficacy in the general population, the general recommendation is that all patients with PID should be vaccinated, especially those with known risk factors for severe COVID-19 (provided that the vaccines are not live attenuated as some patients with PID should not receive these). It is also recommended that their close contacts get vaccinated. Patients / care givers should refer to their national/local recommendations and consult their PID expert physician before receiving vaccinations.
• Patients who were infected with SARS-CoV-2 and have now recovered are still recommended to be vaccinated against COVID-19. Current evidence suggests that reinfection is uncommon within 90 days after the initial infection and vaccination may be postponed until the end of this period.
• For more information: Read the Joint statement on COVID-19, including information on vaccination for patients with PID. (published 28.10.2021).

• A number of studies have been launched with the aim to explore the immune response to natural COVID-19 infection and vaccination in patients with antibody deficiency. Initial findings have found that most PID patients respond to the COVID vaccines, evidenced by the generation of specific antibodies (except in patients with agammaglobulinemia) and T cells. However, the long-term efficacy of the vaccines, and durability vaccine-induced immunity against SARS-CoV2 infection in PID patients, is unknown (same as for the rest of the population).

• Patients (including children) with specific PIDs such as: AIRE deficiency (APS1/APECED), NFkB2 deficiency as well as diseases leading to alterations of the interferon pathways should be highly prioritised for this vaccination.

• Patients (including children) with XLA can be vaccinated with the mRNA-based vaccines or other vaccines (except live attenuated ones). Even though these patients will not be able to mount antibodies against SARS-CoV-2, their T-cells might provide some protection.

• Patients (including children) with predominantly antibody deficiencies can be vaccinated with the mRNA based vaccines or other vaccines (except live attenuated ones). Please refer to your PID expert.

• All PID patients should consult their PID expert physician before receiving vaccinations.
• The majority of PID patients should not take live attenuated vaccines.
• The mRNA vaccines (Pfizer/BioNTech, Moderna) technology is used for the first time for vaccination purposes. These vaccines, as well as the AstraZeneca/University of Oxford vaccine and the Sputnik vaccine should be safe for PID patients who do not have any contraindications (under supervision of a PID expert).

• So far, severe side effects have rarely been reported (except for rare side effects associated with allergies – e. around 1/100,000 infusions and in people with prior history of severe allergies).
• However, it is normal to have certain reactions after a vaccination. There may be redness, swelling, pain around the injection site and/or fever myalgia. These vaccine reactions are usually mild and last only a few days.
• Some vaccines have been linked to very rare but significant severe side effects (specific form of unusual blood clots with low numbers of platelets in the blood), these include AstraZeneca and Janssen vaccines. In both cases the EMA has stated that “The reported combination of blood clots and low blood platelets is very rare, and the overall benefits of the vaccine in preventing COVID-19 outweigh the risks of side effects.”

• The majority of PID patients should not take live attenuated vaccines.
• People with PID may receive mRNA-based vaccines if they have no contraindications to vaccination (under supervision of a PID expert).
• Patients who do not respond to vaccines by measurable antibody titers (such as patients with an antibody deficiency including patients with a profound hypogammaglobulinemia or agammaglobulinemia) should still be considered for vaccination, as the vaccines have been shown to activate the cellular immunity via T-lymphocytes, which may provide a partial protection against COVID-19. This principle also applies to patients who received a therapy against B-lymphocytes (such as rituximab).

• In terms of efficacy, there is no contra-indication regarding the timing of the vaccine and the timing of an immunoglobulin infusion.

• The situation is rapidly evolving with regularly updated vaccine recommendations, including those for children and teenagers. Patients / care givers should refer to their national/local recommendations and PID expert for advice.

• Patients who already had COVID-19 and recovered are still recommended to get vaccinated with a COVID-19 vaccine. Current evidence suggests that reinfection is uncommon within 90 days after the initial infection and vaccination may be postponed until the end of this period (under supervision of a PID expert).

• This is called a “mixed and match” approach and it has mainly been considered due to the problems with vaccine distribution. The discussion has not been related to efficacy.

• PID patients should continue to take the treatment for their PID regularly as well as continue with sensible precautions (social distancing, hand washing).

• Yes, all medications that become available to patients are monitored for many years after commercialization in a so-called phase 4 study (also known as post-authorization safety study).
• These clinical trials study the side effects caused over time by a new treatment, and for side effects that were not seen in earlier trials. They may also study how well a new treatment works over a long period of time.

• Several countries have closed schools to avoid further spread of the virus. Decisions are being made based on the local epidemiological situation and the situation is changing constantly.
• In countries where schools are open or re-opening, the first recommendation is to monitor the latest advice applicable to your area and to always seek advice from your child’s expert physician in case of doubt.
• A general recommendation, in countries where confinement is not required, would be that PID patients continue to go to school, but that the school should ensure that the parents are informed immediately if any of the teachers or classmates present (even mild) symptoms. School attendance will therefore depend on the local epidemiological situation and the underlying PID and needs to be discussed with the PID expert physician.
• If your child goes to school, please ensure they follow appropriate hygiene measures carefully and to monitor and follow your countries national guidelines.

• If a country has started lifting the confinement measures it is because their authorities has made a thorough risk assessment, concluding that it is safe to return to school and work if appropriate hygiene measures are put in place.
• If nothing else is mentioned this also includes PID patients, but we encourage PID patients to seek advice from their PID expert if they are in doubt.
• For PID patients with higher risk for a severe course of the disease it may be considered to continue working from home, to not send the children back to school and to wear special masks (FFP2) for increased personal protection. However, many of these measures present a strong confinement to life and the cost and benefit needs to be balanced.
• It is important to understand that de-confinement measures do not mean that the virus has been extinguished. Confinement has been the strategy in many countries to “flatten the curve” of infections and to avoid overwhelming the health care systems. In many of these countries there is still only a small proportion of the population that has been exposed to the virus so far and de-confinement may lead to a further increase in infections. Hygiene measures and social distancing are still key to protect PID patients after de-confinement.

• Enforced movement restrictions can induce feelings of stress and anxiety for people.
• Remember that it is OK not to be OK but try your best not to panic and keep cool headed. This is especially important for parents with regard to their children.
• Try to eat well and sleep enough.
• Maintain phone and video contact with family and friends.
• If you are in confinement, try your best to keep your brain and body active during this period. Have a routine. Download an exercise app, listen to music, re-read your favorite book, take an online course or clean your home.
• Take breaks from social media and from watching, reading and listening to the news during parts of your day.
• If you feel like you need support, seek advice from a psychologist or follow the advice from your national health authorities.
• More information on how to cope with stress and anxiety available here.

• For PID patients without possibility to isolate, we strongly recommend following guidelines for hygiene: washing hands every hour with soap and water (alcohol based hand rub if soap and water is not available), avoid touching eyes, nose and mouth, avoid public transport, avoid closed spaces, avoid close contact with other people when outside your home.
• For extra precaution, clean and disinfect frequently touched surfaces daily, including tables, doorknobs, light switches, countertops, handles, desks, phones, keyboards, toilets, faucets, and sinks.
• Some countries have taken measures for citizens to wear masks when spending time outside their homes and we advise to follow national guidelines. Masks can be effective to prevent from spreading the disease if the person wearing it has the appropriate training for a good fitting mask, but if not used appropriately they can pose a risk for contamination. The mask needs to be replaced regularly. Guidance from the World Health Organisation on the appropriate way of wearing masks includes:
  – Before putting on a mask, wash your hands (with alcohol-based hand rub or soap and water).
  – Cover mouth and nose with mask and make sure there are no gaps between your face and the mask.
  – Avoid touching the mask while using it; if you do, clean your hands with alcoholbased hand rub or soap and water.
  – Replace the mask with a new one as soon as it is damp and do not re-use singleuse masks.
  – To remove the mask: remove it from behind (do not touch the front of mask)
  – Discard immediately in a closed bin; clean hands with alcohol-based hand rub or soap and water.
• We encourage PID patients to try their outmost to follow the confinement measures
  wherever these are applicable.

• It is very important for PID patients to stay on their Ig treatment, even though it might be administered at the hospital. Generally speaking, it is therefore better to continue receiving the treatment in the hospital rather than to postpone it.
• Some countries have put in place special measures to enable patients who usually get their treatment in the hospital to instead, temporarily, get it at home.
• For PID patients who have this possibility; temporary switching to home treatment is advisable to avoid visiting the hospital and potentially getting exposed to the virus. Home treatment can either be administered intravenously (IVIG) or subcutaneously (SCIG) depending on the country.
• For PID patients who do not have this possibility, clinics should provide a space for PID patients on a dedicated time after the clinic has been closed and properly disinfected. The PID patients should be treated in separate rooms while receiving their treatments.
• PID patients should follow the local health care professional advice in terms of prevention. If a shortage arises and a PID patient cannot access their treatment, then self-confinement and all other preventive measures should be strictly enforced.

• All nurses or health care professionals that visits PID patients in their homes need to be free from COVID-19 symptoms.
• More detailed guidelines (concerning masks, gloves, aprons etcetera) may vary depending on the country and the resources.

• PID patients living in areas of high prevalence should take every precaution and adhere to local, regional and national recommendations such as working from home if possible, avoiding public transport, avoiding closed spaces (e.g. shops) with many people etc.
• Practice social distancing and be especially careful when touching places such as: mobile phones, keys, light switches, doorknobs, elevator buttons, shopping bags etc as the virus can live on these surfaces and the infection may spread.
• Try to eat well and sleep enough.

Keep in mind to:

– Wash hands frequently (every hour) with soap and water for 20 seconds, (if not possible use alcohol-based hand rub), especially after direct contact with ill people or their environment
– Avoid touching eyes, nose and mouth
– Avoid close contact (at least 1 meter/3 feet) with people suffering from acute respiratory infections
– Avoid close contact (at least 1 meter/3 feet) with anyone who has fever and cough
– For extra precaution, avoid close contact (at least 1 meter/3 feet) with all other people when going outside your home
– Avoid greeting people by shaking hands, kissing or hugging
– Respect the confinement measures wherever these are applicable

• PID patients should continue their regular treatment, follow guidelines concerning hygiene and follow national guidelines.
• PID patients should avoid unnecessary travel if not advised in their region. If a trip is necessary and the patient risks not being able to return home, they should ensure that they have a contingency plan prepared for that situation.
• PID patients can get in touch with their national patient organisation and/or IPOPI who may be able to provide the contact details to a local PID expert.

• PID patients should follow their local health care professional’s advice.
• If there is an immunoglobulin shortage and a PID patient cannot access their treatment, then self-confinement and all other preventive measures should be strictly enforced.

• It is very important for PID patients to stay on their Ig treatment and the solution will depend on the local circumstances.
• If a PID patient or their family members experience symptoms and it restricts them from going to the hospital, they should consult their PID expert doctor to see if the treatment can be administered in the patient’s home or if the patient can switch to subcutaneous treatment for a limited period.
• IPOPI monitors the access to Igs and if you experience problems we encourage you to share this information with us by emailing julia@ipopi.org

• In countries where the vaccination programme will take longer to implement or access to treatment is compromised, patients should continue practicing social distancing and frequently wash their hands. They should ensure to continue with the preventive measures for the foreseeable future.

• There is currently no data pointing to whether PID patients are at higher risk of more severe disease from COVID-19.
• The majority of the infected people will experience a mild form of the disease.
• If a PID patient gets infected with COVID-19 the symptoms should be treated.
• PID patients should have prompt phone contact with their local healthcare professional if an infection is suspected and follow their advice (should it be your PID expert, or your GP who should let your PID expert know about your condition in order to provide the best advice for each PID patient’s specific condition).

• PID patients who suspect that they are infected with COVID-19 should have prompt phone contact with a doctor (should it be your PID expert, or your GP who should let your PID expert know about your condition in order to provide the best advice for each PID patient’s specific condition).
• Immediately get medical attention if you experience any of the following symptoms:
  – Trouble breathing
  – Persistent pain or pressure in the chest
  – New confusion or inability to arouse
  – Bluish lips or face
• Please note that this list may not include all warning signs. Consult your medical provider for any other symptoms that are severe or concerning.

• Yes, if an immunologist is available, they should be contacted.
• Not only may the immunologist have additional ideas and advice, but without them being informed there will be no possibility to collect new data. Collecting data is vital to improve the situation for the future.
• IPOPI is currently supporting the data gathering for the COPID global survey on COVID-19 and PIDs, working jointly with the International Union of Immunological Societies and other medical societies.
• Help us by disseminating this survey to your national medical advisers and all national doctors who manage PID patients in your country: https://www.surveymonkey.com/r/67RBPNZ?

• The bacteria in the lungs might create a more severe reaction if a PID patient is infected with SARS-CoV-2, therefore additional antibiotics that would normally be prescribed for a person with bronchiectasis might be an option to try for protection quality. It would be advisable to address this already existing bacteria to possibly reduce the severity of the symptoms caused by the COVID-19
• PID patients should have prompt contact with their local healthcare professional if an infection is suspected and follow their advice (should it be your PID expert, or your GP who should let your PID expert know about your condition in order to provide the best advice for each PID patient’s specific condition).

• The majority of the patients will only have a mild form of the disease and so far, there is no data pointing to whether PID patients are at higher risk of more severe disease from COVID-19.
• Special measures for specific primary immunodeficiencies (CVID, XLA, CGD, WAS, AT, IgG Subclass, IgA def etc.) should be advised by the patient’s PID expert doctor.
• For more information about specific PIDs at higher risk: Read the Joint statement on COVID-19 (published 28.10.2021).
• All PID patients with COVID-19 should monitor the symptoms closely, keep their PID expert doctor informed about their status and follow their advice.
• All PID patients should keep the details of their PID diagnosis and medical charts, medications, PID expert doctor and next of kin at hand, in case urgent medical care is needed.
• For PID patients who have tested positive for COVID-19, it is recommended to perform a second screening after the patient has clinically recovered, as it may be that some PID patients might struggle with clearing the infection. These patients may remain positive longer and risk remaining a source of infection to their environment.

• Recent studies have been looking at the levels of SARS-CoV-2 neutralizing antibodies in IG therapies as the pandemic has evolved. Most recently very high SARS-CoV-2 antibody titers have been described in the literature. This is due to the fact that an increasing proportion of the general and therefore plasma donors’ population, now carries SARS-CoV-2 neutralizing antibodies, a consequence of either earlier COVID-19 or from vaccination against it.
• The study shows that a proportion of immunoglobulin lots fractionated from US-origin plasma now contain higher doses of SARS-CoV-2 neutralizing antibodies than earlier used for therapeutic treatment of COVID-19 by convalescent plasma.
• Given the fact that the typical time interval between plasma collection and final IG lot release is 7-10 months, it can be expected that plasma collected now would contain higher SARS-CoV-2 neutralizing antibody titers, which should result in a further increase of SARS-CoV-2 neutralizing potency of IG therapies in the coming months.
• Whilst these are encouraging news for PID patients, it is important to point out that the clinically protective dose of IG has not been established and that more observational studies are needed at this stage to be able to draw new potential recommendations in this regard. PID patients on IG replacement therapies should therefore continue to take all additional precautionary and protective measures and follow all recommendations outlined in this statement, their treating physician, and relevant national guidelines.

• There is a belief that T-cells might play a role in the immune response against SARSCov- 2 and as these functions very well for XLA patients it is possible. However, it is too early to say how this will affect these patients as the data is not yet available.
• Studies show that specific antibodies against SARS-CoV-2 are generated after a COVID-19 infection, but further research is needed to establish if this will result in long-term immunity.

• If someone in your family gets infected the likelihood that the disease will be transmitted to the patient increases, despite properly following hygiene measures.
• It is encouraged to clean and disinfect high-touch surfaces daily in household common areas (e.g. tables, hard-backed chairs, doorknobs, light switches, phones, tablets, touch screens, remote controls, keyboards, handles, desks, toilets, sinks)
• In the bedroom/bathroom dedicated for an ill person: consider reducing cleaning frequency to as-needed (e.g., soiled items and surfaces) to avoid unnecessary contact with the ill person.
• As much as possible, an ill person should stay in a specific room and away from other people in their home, following home care guidance.
• More information available at the Center for Disease Control and Prevention website

• There is still very little that we know about COVID-19, especially concerning why the syndrome is so devastating in some populations – but not in others.
• Another area where more research is needed concerns the long-term effects of covid-19, especially the long-term effects of the hyperinflammation.

• It is misleading to speak about a peak as it is often associated with an expected decline. Instead, based on current epidemiological data across the world, we should refer to it as reaching a plateau where the level of contamination continues to be high but does not increase.
• There may still be a high number of new cases each day, but when reaching the plateau these numbers will not increase nor decrease for an extended period of time.
• There are a number of countries who have reached this plateau. Depending on the confinement exit strategies put in place, this may be followed by a decline in infections.
• It is important to understand that de-confinement measures may lead to a further increase in infections and that patience and caution will be needed.

• We may only see a permanent restriction of the circulation of the virus when reaching a higher level of immunity in the population.
• The most important factor to restrict the circulation of the virus are the vaccines.

• Studies show that specific antibodies against SARS-CoV-2 are generated after a COVID-19 infection, but further research is needed to establish if this will result in long-term immunity.
• However, based on experiences from MERS-CoV and SARS-CoV-1 (previous coronaviruses), it is likely that patients who recover from SARS-CoV-2 will develop long-term, but not life-long, antibodies.

• To date (28-10-2021), global surveys aimed at collecting data on COVID-19 in PID patients do not point to an increased risk of COVID-19, especially not in its severe form, although some cases have been reported. However, certain PID patients might be at higher risk than others to be infected or develop a more severe course of disease and patients with PIDs should take extra care to avoid getting this infection.
• For more information about specific PIDs at higher risk: Read the Joint statement on COVID-19 (published 28.10.2021).

• Yes there are many ongoing studies.
• For more information about some of these: Read the Joint statement on COVID-19 (published 28.10.2021).

• It’s not the first SARS virus outbreak, there were two before in the previous years, one called SARS-CoV and the other MERS-CoV, and there will likely be other SARS virus outbreaks in the future. It is not yet possible to say if this will be the same kind of viral infection, but we will need to live with this current virus in the next years.

• Yes, in these regions they will have to fight both viruses.
• To ensure protection against influenza viruses, it is recommended that most PID patients and their families be vaccinated against seasonal flu by inactivated vaccines.
• Please note that recommendations will vary between PID patients and specialist advice should always be sought before receiving vaccinations.
• More info on PID and vaccination available here.

• The decline in blood and plasma donations observed in 2020 now estimated at 20% has continued in 2021 due to the COVID-19 outbreak and associated confinement and movement restriction measures. This has had an impact on the supply of life saving plasma derived medicinal products such as IG therapies. Because it usually takes 7-10 months from the time plasma is collected from a human donor to reach the patients, the consequences of the decrease in plasma collection on supply of IG therapies have been manifesting in recent months with varying degree in different countries and are expected to continue in the coming months.
• Various PID stakeholders, such as the Supply and Access for Everyone (SAFE) taskforce, are currently taking measures to react to this development on both national and regional levels so that PID patients are prioritized in case of any supply tensions or shortages associated with the COVID-19 outbreak IPOPI and other PID stakeholders are taking measures to react to this development.

• Yes, various PID stakeholders, such as the Supply and Access for Everyone (SAFE) taskforce, are currently taking measures to react to this development on both national and regional levels so that PID patients are prioritized in case of any supply tensions or shortages associated with the COVID-19 outbreak IPOPI and other PID stakeholders are taking measures to react to this development.
• We encourage our national member organisations to advocate in their national settings.

• Each day we learn more about the development of this pandemic and what needs to be put in place, so by the time of a possible second wave we should be better equipped to respond to it.
• Since the start of this pandemic IPOPI has been working on various fronts to ensure that the voice of PID patients is included and consulted in the areas that affect them. A brief list of measures taken so far:
  – IPOPI has released an open letter with a call to authorities to ensure sufficient blood and plasma supply during and after the COVID-19 outbreak. National member organisations (NMOs) are encouraged to translate this letter and use as a tool when advocating in their national setting. If your NMO would like to use the open letter but you have doubts on how, don’t hesitate to contact us so we can help you tailor the approach.
  – IPOPI has offered the opportunity for NMOs to participate in Webchats with PID experts responding to questions on COVID-19. Are you active in one of our member organisations and would like to learn more? Send an email to julia@ipopi.org for more info.
  – Launch of IPOPI’s online awareness campaign #ICountOnYou with 31 participating countries from all over the world. This 8-day campaign highlighted the need for social distancing and plasma donation to ensure that PID patients are being kept safe now and in the future.
  – The Platform of Plasma Protein Users (PLUS) where IPOPI is represented has sent an open letter to the EU Ministers of Health on the need for a continued access to plasma-derived medicinal products and for strengthening the collection of blood and plasma.
  – Publication of PLUS statement on access to homecare & plasma derived medical products during COVID-19.
  – IPOPI is one of the stakeholders consulting the European Commission and the European Centre for Disease Control (ECDC) on the update of the previously released ECDC report on Substances of Human Origin.  The 1^st update was released on 29 April.
  – IPOPI are co-signatures to a letter by the American Plasma Users Coalition (APLUS) to the US Department of Health to ensure that the new new Centers for Disease Control and Prevention’s mask wearing policy will not impact plasma collection centres capacity to collect plasma.
  – IPOPI actively takes part in discussions with the Plasma Protein Therapeutics Association (PPTA) through their stakeholders online meetings and continuously monitors the development regarding a decline in plasma collection.

• IPOPI’s Medical Advisory Panel, comprising medically qualified specialists in primary immunodeficiencies, is at disposal for PID & COVID-19 specific medical questions.
• The European Society for Immunodeficiencies (ESID) also provides a virtual space where junior doctors can ask for PID expert advice.
• Additional advice can be sought from the COPID19 team, responsible for launching the ongoing Worldwide survey of COVID-19 in PID patients.