Important Update SymbolQuestion: My patient 60 yr old female has CVID, and is stable on four years of IVIG therapy. She did have mild bronchiectasis which has mostly resolved on Chest CT, and had a history of recurrent sinus and lung infections prior to IVIG but these have been rare since being on IVIG. She had COVID-19 infection recently with diarrhea, reduced appetite and fatigue, and has been working from home. Her employer has asked her to return to in person as they are assuming she has immunity. My question is how reliable is a COVID-19 IgG antibody level in a patient with CVID? Do we have evidence of normal immune response? What about response to vaccine? I assume there will be recommendation to vaccinate those with CVID? Also, as an aside, are patients with selective IgA deficiency at more risk for COVID-19?

Answer: Regarding patients with CVID, those on regular immunoglobulin replacement appear to have a milder clinical course. In April 2020, Quinti et al, postulated complete B cell depletion (such as in XLA) may actually be a protective factor (1). This hypothesis was further strengthened by another report of two XLA patients with mild COVID-19 courses (2). There are reports of COVID -19 related fatalities in patients with CVID, but a review of literature suggests that this is likely the exception rather than the rule. The majority of patients with CVID who have therapeutic IgG levels will likely have a benign clinical course.

Antibody testing will not be reliable in patients with CVID. Some reports indicate patients with CVID did not have detectable SARS-COV2 IgG antibody responses despite having PCR positivity. Further, a positive SARS-COV2 IgG could be reflective of the IVIG donor rather than the patient herself (as infection rates climb precipitously in the United States). A recent study published that the seroprevalence in the general population in the US is <10%, so at best there would be limited IVIG donors that have anti-SARS-COV2 antibodies (5)

It appears that both RNA and adenovirus vaccines are safe for patients with CVID, although their efficacy in this population is unknown. Dr. Kate Sullivan has been providing fantastic COVID-19 related updates on the Immune Deficiency Foundation website. See here for her most recent video regarding vaccination.

In terms of selective IgA deficiency, there has been a case report of a patient developing complications of COVID-19 (6) and a Japanese report suggesting a strong positive correlation between frequency of selective IgA deficiency and the rate of COVID-19 infection in the community. These authors suggested the extremely low frequency of selective IgA deficiency in Japan versus the US (40 times more in the US) may explain higher mortality in the United States (7). However, these are very preliminary data and should be viewed cautiously.

Patients with humoral immunodeficiency appear to mostly have mild disease. Additional risk factors such as obesity, other medical co-morbidities as well as subtherapeutic IgG levels seem contribute towards a more complicated clinical course. There is continued need to gather additional data regarding this vulnerable patient population, but at present, we can continue to provide reassurance and encourage social distancing, wearing masks and frequent hand washing.

1. Quinti I, Lougaris V, Milito C, et al. A possible role for B cells in COVID-19? Lesson from patients with agammaglobulinemia. J Allergy Clin Immunol. 2020;146(1):211-213.e4. doi:10.1016/j.jaci.2020.04.013

2. Soresina A, Moratto D, Chiarini M, Paolillo C, Baresi G, Focà E, Bezzi M, Baronio B, Giacomelli M, Badolato R. Two X-linked agammaglobulinemia patients develop pneumonia as COVID-19 manifestation but recover. Pediatr Allergy Immunol. 2020 Jul;31(5):565-569. doi: 10.1111/pai.13263. Epub 2020 May 19. PMID: 32319118; PMCID: PMC7264678.

3. Fill L, Hadney L, Graven K, Persaud R, Hostoffer R. The clinical observation of a patient with common variable immunodeficiency diagnosed as having coronavirus disease 2019. Ann Allergy Asthma Immunol. 2020;125(1):112-114. doi:10.1016/j.anai.2020.04.033

4. Mullur J, Wang A, Feldweg A. A fatal case of coronavirus disease 2019 in a patient with common variable immunodeficiency [published online ahead of print, 2020 Aug 18]. Ann Allergy Asthma Immunol. 2020;S1081-1206(20)30573-1. doi:10.1016/j.anai.2020.08.017

5. Bajema KL, Wiegand RE, Cuffe K, et al. Estimated SARS-CoV-2 Seroprevalence in the US as of September 2020. JAMA Intern Med. Published online November 24, 2020. doi:10.1001/jamainternmed.2020.7976

6. Pfeuffer S, Pawlowski M, Joos GS, et al. Autoimmunity complicating SARS-CoV-2 infection in selective IgA-deficiency. Neurol Neuroimmunol Neuroinflamm. 2020;7(6):e881. Published 2020 Aug 12. doi:10.1212/NXI.0000000000000881

7. Naito Y, Takagi T, Yamamoto T, Watanabe S. Association between selective IgA deficiency and COVID-19. J Clin Biochem Nutr. 2020;67(2):122-125. doi:10.3164/jcbn.20-102

Question: A 47 year-old white female with a past medical history of recurrent infections years ago has had an immune evaluation reveal normal QIA with inadequate response to pneumococcal titres. She was treated with IgRTx until December when she decided it was inconvenient and it was discontinued. She has done well without recurrent infections. She is employed as a teacher and is concerned she may become infected with COVID-19 and requested she resume IgRTx. Repeat immune work up revealed persistently normal QIA and only 3/23 pneumococcal titres protective. In addition to resuming IgRTx she requests a letter for short term and possibly long-term disability. In the absence of recurrent infections, I will not resume the IgRTx, however how likely is she to become infected with COVID-19 and have a poor outcome? Does she need to remain out of school for the duration of the pandemic?

Answer: There is no data to support the assertion that a patient with inadequate pneumococcal titers would be at increased risk for contracting COVID-19. We are not aware of any data that would support the off-label use of replacement IgG therapy to lower one's risk of contracting COVID-19. In addition, COVID-19 antibodies are not likely to be present in current immunoglobulin products, so resumption of IgRTx would not be helpful in reducing her risk of infection and isn’t otherwise indicated based on the absence of recurrent infections.

Question: Any thoughts on a 37y/o pediatric nurse, recently diagnosed with CVID and on SCIG for 3 months, returning to work? She has had a very good response to treatment with normalization of IgG and significant reduction in Chronic Sinusitis and respiratory symptoms. At work she has been restricted from patient care and is essentially doing telephone duties. She and her employer are anxiously wanting her to return to working “well child visits”. I have been asked for guidance in clearing her to return to direct patient care. Are there any recommendations for health care workers with CVID working with patients? I am in an area that is currently considered a hot spot.

Answer: We don’t have a lot of data on CVID patients and the risk for COVID-19 infection or the severity of infection, but what we do have is reassuring.  CVID patients have generally fared well during this pandemic.  Studies reported on infections from various hot spots (China, Italy, US) have not included very many patients with CVID, suggesting that they are not at increased risk of severe disease, and patients with CVID generally do well with viral infections, unless they have a significant problem with T cell immunity.  Whether this patient is able to return to work or not is dependent on factors that would relate to any individual who would like to return to work during the pandemic.  What is the current transmission rate in the community in which they are going to work? What is the capability of the practice to protect the person, and what will their role be in the work?  General pediatric practices in areas in which there is high community transmission of the virus should be considering performing virtual well child visits.  Does the practice screen patients before they are allowed into the office?  Does the office have the capability to provide physical distancing?  Does the office have adequate amounts of PPE to protect their staff?  What is the “culture of safety” within the office, meaning what sort of precautions do staff members take outside of the office?  If the answers to these questions are reassuring, then your patient can most likely return to work.

Question: A 23 y/o patient with CVID diagnosed solely on poor response to childhood vaccines (while in nursing school) and poor studies of functional antibody response has not had any serious infection problems, and is on IG replacement therapy. She currently works as a nurse in a small hospital. Two questions – with COVID-19 what are hazards of her working in hospital with CVID and no history of recurrent or severe infections? She is not going to respond to COVID-19 vaccine when it is available. She will get passive COVID-19 immunity as more are vaccinated (when available).

Answer: Viral disease is generally not as much of a problem as bacterial infection with humoral immunodeficiency including CVID, IgG subclass deficiency and functional antibody deficiency. There are exceptions, such as enteroviral infections, and disseminated viral disease in CVID with significant T cell abnormalities, but in general viral disease is not the clinical problem. 

I would not consider your patient at significant increased risk working in a hospital since she is receiving gamma globulin and has no history of infections. The experience with immune suppressants, as used in rheumatologic and other autoimmune conditions, is treated subjects are not experiencing much greater disease severity. Generally, the problems with immunosuppressants/immunomodulators is atypical infections or systemic viral disease and not viral respiratory viral illness. Whether this applies to COVID-19 is not clear but there is no compelling evidence of increased risk.

I disagree she will not respond to a COVID-19 vaccine based upon her clinical status (unclear diagnosis of CVID, especially given the lack of any infection history). Giving gamma globulin would mitigate responses to vaccines for which there is significant antibody specific for the immunogen in the gamma globulin, but this is not the case for SARS-CoV-2. Furthermore, there is not sufficient information to assess how she may respond to a possible COVID-19 vaccine and there is no totally agreement on what characterizes an immune response. Therefore, she may or may not respond but I would posit she will benefit similarly to other adults.

Perez, Elena, et al. "Specific antibody deficiency: controversies in diagnosis and management." Frontiers in immunology 8 (2017): 586.

Bonilla, Francisco A. "Update: vaccines in primary immunodeficiency." Journal of Allergy and Clinical Immunology 141.2 (2018): 474-481.

Ameratunga, Rohan, et al. "Diagnosing common variable immunodeficiency disorder in the era of genome sequencing." Clinical reviews in allergy & immunology 54.2 (2018): 261-268.

Marsh, Rebecca A., and Jordan S. Orange. "Antibody deficiency testing for primary immunodeficiency: A practical review for the clinician." Annals of Allergy, Asthma & Immunology 123.5 (2019): 444-453.

Lebwohl, Mark, Ryan Rivera-Oyola, and Dedee F. Murrell. "Should biologics for psoriasis be interrupted in the era of COVID-19?" Journal of the American Academy of Dermatology 82.5 (2020): 1217-1218.

Blaszczak, Alecia, John CL Trinidad, and Alexander M. Cartron. "Adalimumab for treatment of hidradenitis suppurativa during the COVID-19 pandemic: Safety considerations." Journal of the American Academy of Dermatology (2020).

Patruno, Cataldo, et al. "Dupilumab and COVID‐19: what should we expect?" Dermatologic Therapy (2020).

Question: Have a 10 y/o female patient with selective IgA deficiency - no recurrent infections, no autoimmune disease - mild asthma. Mother very concerned about COVID-19 exposure and potential for severe course if exposed. When schools open in fall, mother asks about home school until vaccine available. Would this be a reasonable consideration or could she safely (as much as other children) return to school exposure with safety precautions in place?

Answer: Since the COVID-19 pandemic is a dynamic situation and information is constantly evolving, it is near impossible to make definitive recommendations regarding events in the Fall. Also, we are still gathering data regarding patients with primary immunodeficiency and their risk factors for contracting SARS-CoV2 or having a more severe disease course. A few organizations have put out guidelines for patients with PID. They include: Working Group for Pediatric Immunology (API) from Europe and International Patient Organization for Primary Immunodeficiencies (IPOPI).

It is important to note that not all immunodeficiencies are equally susceptible to the infection/complications related to SARS-CoV2. In the case of your patient, she has a history of selective IgA deficiency, which in general has a milder phenotype. Given the absence of infections, autoimmunity and only mild asthma, per API guidelines, this patient would likely follow a similar course as that of a patient WITHOUT immunodeficiency. In addition, IPOPI provides the following recommendations:

  • "If a country has started lifting the confinement measures it is because their authorities have 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. Please ensure to follow appropriate hygiene measures carefully and to monitor and follow your countries national guidelines."
  • The decision regarding return to school would depend on local disease prevalence in the Fall and adherence to medical recommendations by the general public as well as the local schools. In addition, new information may emerge specifically regarding PID patients over the next few months that could alter recommendations.
  • At this juncture, the expert consensus would be to allow a patient with selective IgA deficiency to attend school if proper measures are in place. Though the risk for severe complications exists, it is not yet clear what the risk factors are for a more severe disease course in pediatric patients. So far, selective IgA deficiency has not been identified as a risk factor, though it is the most common PID. Given the marked anxiety surrounding the COVID-19 pandemic, we recommend shared decision making which would involve providing the families with the available information/recommendations, but also taking the individual family's fears and concerns into account.

Here are links to the guidelines mentioned:

Additionally, these websites may also provide helpful information about PID and COVID-19.
For patients: Immune Deficiency Foundation COVID-19 Resource Page
For providers: Clinical Immunology Society COVID-19 Resources

Question: Is there anything we should know in regards to immunocompromised patients since they are in a high-risk category when it comes to COVID-19?

Answer: The published data from China has very few immunodeficient patients included in their cohorts, for example, out of 1,066 hospitalized there were two, and they had non-severe disease (NEJM 2020. DOI: 10.1056/NEJMoa2002032). Nonetheless, it makes sense that patients who have compromised immune systems will be at risk of a more severe infection, if they get COVID-19. The importance here is to prevent infection in the first place. As has been said numerous times, the best approach at this time is for these patients to: (1) practice social distancing (avoid crowds and travel, keep at least six feet away from anyone who appears ill), (2) frequently wash their hands with soap and water for 20 seconds, and don’t touch your face, (3) continue any medications for their underlying health conditions, and (4) call before going to any healthcare provider (including emergency department and urgent care). The last issue is important because providers need to make sure that when an immunocompromised patient comes to their office they are not exposed to potential COVID-19 patients. Providers should keep a close eye on their own health and take appropriate precautions to not become infected with SARS-CoV-2, and to stay at home should they exhibit signs of COVID-19.

Question: I have a patient recently diagnosed with CVID. She has no ability to make antibodies at all, and is now receiving IVIG. For COVID-19, even if a vaccine becomes available in the fall, are there any antiviral medication regimens you would recommend at this juncture to utilize prophylactically or maintain on standby if required?

Answer: At this point there is no proven effective therapy for COVID-19. There are a number of clinical trials ongoing. Social isolation is key in this setting. Anti-COVID 19 IgG will eventually make its way into IVIg materials, but this will take several years at a minimum. This is a very difficult problem. You will also find information on this topic in the Special Article: COVID-19: Pandemic Contingency Planning for the Allergy and Immunology Clinic


Some answers have been updated to reflect changing circumstances and information since the individuals submitting the questions were originally provided with a response. While we’re working on keeping answers updated as best we can, information continues to evolve rapidly. Please email us at with concerns or additional questions.