This document discusses COVID-19 in immunocompromised patients. It notes that while immunocompromised patients are at higher risk of severe COVID-19 due to an impaired immune response, the suppression of inflammation may also be protective. The effects of various immunocompromising conditions like HIV, cancer, transplant recipients, and primary immunodeficiencies on COVID-19 outcomes are reviewed. Management strategies like antiviral therapy and immunoglobulin replacement are also discussed. More research is still needed to understand how immunocompromise impacts COVID-19 severity.

1. Covid 19 in immunocompromised
patients
Fawzia Abo Ali
Prof. of Allergy & clinical Immunology
Ain Shams faculty of medicine

2. • COVID-19 disease leads to severe acute
respiratory syndrome caused by
coronavirus 2 (SARS-CoV-2)
• Since 31 December 2019 and as of 09
August 2020, 19 624 044 cases of COVID-
19 including 726 953 deaths.
• The public has been barraged by
conflicting messages because it is a new
and still poorly understood virus
(infodemic)

3. According to the Centers for Disease Control and Prevention,
SARS-CoV-2 is more likely to cause severe disease in:
• People older than 65 years old,
• Those with comorbid conditions
• Immunocompromised patients:
• patients with primary immunodeficiency.
• patients with human immunodeficiency virus (HIV) infection
• patients with cancer or hematologic malignancy,
• solid-organ transplant (SOT) recipients,
• patients taking biologics & immunosuppressive therapy.

4. Important questions crucial to our understanding of
immunocompromised patients with COVID-19 .
Do immunosuppressed patients have more severe COVID-19 outcomes?
 or, conversely, are they protected from cytokine-mediated inflammation
and therefore severe disease?
do immunocompromised patients have atypical clinical manifestations?
What is the attributable risk of immunosuppression versus other
comorbidities on COVID-19 severity??

6. Fate of covid 19

9. COVID-19 and immunocompromised patients
• the biological response to SARS-CoV-2 infection requires
the activation of the innate and acquired immunity.
• the overactivation of T cells, manifested by increase of
Th17 and high cytotoxicity of CD8+T cells, were related
with the severe lung immune injury.
• So the effects of immunosuppression may be protective,
modifying the “cytokine storm” related to COVID-19 poor
outcomes
• The interplay between the viral load and active
inflammatory response of immune system decide who
will win finally

10. Covid 19 in immunocompromised hosts:
• The clinical features and outcomes of COVID-19 among
immunosuppressed patients are not well understood.
• Some studies have reported an overall asymptomatic or mild COVID-
19 course in immunocompromised patients, such as children under
anticancer therapy, , immunosuppressive chronic drugs
users, transplant recipients, and poorly controlled HIV or AIDS
patients.
• In these reports, the few severely affected individuals recovered and
low fatality rates were registered.

11. Taming of the shrew:
• However, the association between
COVID-19 and intense cytokine release
(cytokine storm and secondary
hemophagocytic lymphohistiocytosis
syndrome) ,raises the possibility that
immunosuppression may actually
temper the accompanied excited
inflammatory response .

12. Primary Immunodeficiency: PAD
• Agamaglobulinemia
• CVID
• Selective IGA deficiency

13. Primary Immunodeficiency: PAD
• PAD patients are vulnerable to most bacterial and to a limited number
of viral infections .
• Agammaglobulinemia patients had a milder course with COVID-19,
suggests a role of B lymphocytes in the SARS-CoV-2 induced
inflammation.
• Potientially the lack of B cell-derived IL-6 abrogates the risk of
cytokine storm that is associated with poorer outcomes.
• These observation suggests that immunoglobulin levels are not
predictive, but B lymphocyte number (agammaglobulinemia) or
function (CVID) may be critical

14. • CVID patients (n=5) presented with a severe COVID infection requiring
multiple drug treatment, including antiretrovirals agents and IL-6
blocking drugs, and mechanical ventilation.

15. Considerations applied to PAD
• Minimize the viral load (isolation)
• Maintain IVIG & serum igg level.
• Provide proper antibacterial and antiviral therapy.
• Avoid early administration of immunosuppressive drugs

16. Reported ttt strategy in covid pts.
1. intravenous immunoglobulin replacement
• hydroxychloroquine (200 mg twice a day),
• azithromycin (500 mg once a day),
• darunavir/cobicistat (800/150 mg once a day).
2. paracetamol, ibuprofen, amoxicillin/clavulanic acid,
and levofloxacin. lopinavir/ritonavir 200/50 mg, 2 capsules twice a
day), hydroxychloroquine (200 mg twice a day), and ceftriaxone
(because of a previous allergic reaction to azithromycin).

17. • 3.vancomycin, meropenem, linezolid, caspofungin, with prednisone
(25 mg per day) and subcutaneously injected immunoglobulins
and ​oral steroids,
• ​Therapy with lopinavir/ritonavir (400/100 mg once a day),
azithromycin (500 mg once a day), and hydroxychloroquine (200 mg
twice a day) was started.
• 4. The patient received immunoglobulin replacement treatment at a
rate of 400 mg/kg per dose every 4 weeks He started receiving
lopinavir/ritonavir (400/100 mg once a day), hydroxychloroquine (200
mg twice a day), and piperacillin/tazobactam.
• tocilizumab (8 mg/kg per day) was started. After 2 days of mechanical
ventilation, the patient was switched to remdesivir (200 mg
intravenously once a day) (on the first day) followed by remdesivir
(100 mg intravenously once a day

18. Selective IgA deficiency:
• 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, taking the individual family's
fears and concerns into account.
• Diarrhea and other gastrointestinal symptoms occur in more than
10% of people with SARS-CoV-2 infection.
• However, recent studies revealed that once respiratory infections
occur, 20% to 30% of them develop severe symptoms.
• Areas of high prevalence have high mortality.

19. Patients taking corticosteroids
• low-dose corticosteroids do not seem to affect the incidence of
serious infections in patients.
• High dose steroids, Although there is a concern for increased risk of
viral infections if given early, While corticosteroids may blunt or
inhibit the immune response, the tissue damage may be decreased by
corticosteroid use.

20. HIV/AIDS
• People living with HIV and on effective antiretroviral treatment (ART)
are not at greater risk of getting coronavirus.
• People living with HIV who have a compromised immune system
should be extra cautious to prevent coronavirus infection.
These include people with
• a low CD4 count (<200 copies/cell),
• a high viral load,
• or a recent opportunistic infection
• older people(As with the general population) living with HIV should
take extra precautions to prevent illness.

21. Diabetes mellitus
Many studies on COVID-19 have reported diabetes to be associated
with severe disease and mortality,

23. • SARS-CoV-2 affects circulating
immune cells (CD3, CD4, and CD8 T
cells) inducing apoptosis of
lymphocytes ,lymphocytopenia :
• Suppression of the innate immune
system
• overproduction of pro-
inflammatory cytokines (TNFα, IL-6,
IL-1β, and CXC-chemokine ligand
10)
• prothrombotic state
• diabetes is already characterised by
low-grade chronic inflammation.
• A dysregulated inflammatory innate
and impaired T lymphocyte immune
response.
• High blood concentrations of
inflammatory markers (ie, C-reactive
protein, procalcitonin, and ferritin), a
high neutrophil-to-lymphocyte ratio,
and increased blood concentrations
of inflammatory cytokines
• prothrombotic state.
Immunoinflammatory state in both SARS-CoV-2 and
diabetes :

24. Effect of Age
• One of the risk factors most strongly associated with severe COVID-19
and death is advanced age.
• Immunosenescence present in the elderly affects innate immunity
• reducedT cell-dependent adaptive responses .
• In addition, documented evidences that elderly have increased levels
of proinflammatory cytokines

25. Sex difference

26. pregnancy

27. Home message
• Since COVID-19 is a new disease, knowledge about this disease is still
incomplete and evolving.
• current best practice guidelines worldwide recommended the
continuation of immunosuppression treatment in patients who
require them cautiously .
• the immune system is a double-edged weapon, that has balance
between its primary activity of defense against foreign pathogens,
and hyperinflammatory status.
• Covid 19 has unique immunoinflammatory pathogenesis

28. • The clinical features and outcomes of COVID-19 among
immunosuppressed patients, who are at presumed risk of more
severe disease but who may also have decreased inflammatory
responses, are not well studied.
• As Preliminary clinical experiences showed that morbidity and
mortality rates in immunosuppressed patients may not differ largely
from the general population,Yet a lot of precautions should be
considered in these situations
• As more people become infected with coronavirus, we will learn more
• Overall, further prospective controlled studies are needed to
determine the attributable risk of immunocompromising conditions
and therapies on COVID-19 disease prognosis.