Table 2 COVID-19 mortality in patients with immunodeficiency and its predictors

1

Bhaskaran K [17]

N = 17,282,905 [HIV-infected N = 27,480 (0·16%)]

Median = 48 (40–45)

Male (n = 17780 (64.7%)

–

HIV

–

Current or former Smoker (51.2%)

Hypertension (19.3%)

Chronic respiratory disease (4.0%)

Cardiovascular disease (3.4%)

Stroke or dementia (2.0%)

Other neurological disease (0.9%)

Organ transplant (0.3%)

Asplenia (0.3%)

RA, lupus, or psoriasis (4.5%)

Other immunosuppressive (0.2%)

Diabetes mellitus (9.8%)

non-hematological cancer (4.7%)

Hematological malignancy (2%)

chronic Renal failure (0.5%)

HIV-infected patients have higher risk of COVID-19 death: hazard ratio (HR) = 2·90

the association was larger in Black individuals (HR = 4·31)

0.09%

2

Cabello A [18]

N = 18853(HIV-infected = 63)

Median = 46 (37–56)

Male n = 56 (88.9%)

–

HIV

Lymphopenia (26.5%) Ferritin > 1000 mcg/L (25%)

D-dimer > 2500 ng/mL (4.8%)

CD4 +  < 200 cells/µL (6.3%)

Nadir CD4 < 200 cells/µL (25.4%)

HIV infection time (years) = 10.8

ART N = 61(96.8%)

virological suppression time (years) = 7.2

Current or former Smoker (48.2%)

COVID-19 diagnosis: laboratory confirmed (49.2%), clinically suspected (50.8%)

duration of symptoms (days) before treatment = 6

Pneumonia (47.5%)

WHO COVID-19 severity score (28.6%)

Hospital admission (32.3%)

Previous comorbidity (84.1%)

Hypertension (19%)

Diabetes mellitus (9.5%)

Overweight 13.1%

cardiovascular disease (12.7%)

Chronic respiratory disease (4.8%)

chronic Renal failure (3.2%)

COVID-19 Prevalence in HIV-patients = 1.68%

HIV-related factors did not show association with the severity of COVID-19

3.17%

3

Childs K [28]

N = 18

Median = 52(49–58)

Male n = 12 (67%)

–

HIV

Preadmission CD4 count, cells/µL = 395

Nadir CD4 count, cells/µL = 97

HIV RNA < 50 copies/ml = 17(94%)

Lymphocytes = 1100

CRP = 143 (72–253)

HIV infection time (years) = 14.6

Smoker = 0 (0%)

duration of COVID-19 symptoms at admission (day) = 8

Cough (72%) Dyspnea (67%) Fever (61%)

Pneumonia (72%)

AKI (28%)

requiring mechanical ventilation = 5 (28%)

Obesity (BMI > 30 kg/m²) (56%)

Hypertension (33%)

Diabetes mellitus (22%)

Chronic kidney disease (28%)

COVID-19 impose more morbidity and mortality on HIV-infected patients

27.8%

4

Cohen B[19]

N = 135 N = 10 (COVID-19 positive)

37

Male = 6 (60%)

CVID

–

Lymphopenia 3 (30%)

Pneumonia (0%)

requiring mechanical ventilation = 0 (0%)

mild to moderate symptoms = 9 (90%)

on biological therapies = 2(20%)

Previous comorbidity (HTN, DM) = 3 (30.0%)

All the patients recovered

CVID patients are not at a higher risk for mortality and worse outcome

0%

5

Del Amo J [32]

N = 77,590 (HIV-infected persons receiving ART) N = 236 (COVID-19 positive)

48.9

Male = 58,120 (75)

–

HIV

–

Hospital admission 151 (64%)

median duration of hospitalization for discharged patients (day) = 7 (4–10)

ICU admission 15 (6%),

death: 20 (8%)

–

Standardized risk per 10,000 between the 77,590 HIV-positive persons

 = 30.0 for COVID-19 diagnosis

 = 3.7 for death

greater risk in men and age > 70 years

lower risk (= 16.9) for TDF/FTC regime

incidence of COVID-19 in HIV infected population is comparable to the normal population

TDF/FTC treatment may have beneficial impact for patients with COVID-19 and HIV co-infection

8%

6

Delavari S [24]

N = 2754 with primary immunodeficiencies (PIDs) N = 19 (0.68%, PIDs with COVID-19 positive)

9

Male = 1756 (63.8%)

Primary immunodeficiencies (PIDs):

Combined immunodeficiencies (n = 1392)

humoral immunodeficiencies (n = 1391)

phagocytic defects (n = 782)

immune dysregulation (n = 117)

autoinflammatory disorders (n = 734)

complement deficiency and innate immunodeficiencies (n = 304)

–

Negative acute-phase reactant proteins = 8 (42.1%)

Requiring respiratory support = 10 (52.6%)

bronchiectasis 4 (21.0%)

cardiovascular complications 2 (10.5%)

liver failure 2 (10.5%)

pulmonary complications (varied from mild prominence of broncho-vascular markings to mucus plugging, prebronchial thickening, diffuse patchy opacities, collapse/consolidations, mosaic perfusion, and ground glass interstitial disease, based on the severity of diagnosed PID)

history of lower respiratory tract infection before COVID-19 (89.4%)

lymphoproliferation = 7 (36.8%)

1.23 folds higher risk of COVID-19 infections (0.68%)

Tenfolds higher mortality rate (0.003%)

most mortality rate of COVID-19 infection: SCID patient (0.03%) and FHL (0.027%)

42.1%

7

Fill L [25]

A CVID COVID-19 positive patient (confirmed by PCR)

53

Female

CVID

–

Leukopenia (2800 cells/µL)

Lymphopenia (770 cells/µL)

CBC, electrolytes, renal and liver function, and serum procalcitonin = in the normal range

CRP = 16.6 mg/dL

IgG = 1710 mg/dL (normal)

IgM = 33 mg/dL (low)

IgA < 7 mg/dL (undetectable)

duration of COVID-19 symptoms at admission (day) = 7

chest CT-scan = multifocal ground-glass opacities

Admission to ICU (day 4)

Mechanical ventilation (day 7)

ARDS

CVID

breast cancer

hypothyroidism

Sjogren’s syndrome

–

recovered

8

Gamboa E [38]

A co-infection of HIV and COVID-19 case (confirmed by PCR)

59

Male

–

HIV

Undetectable viral load

CD4 + cells/µL = 507

the progressive decline of CD4 + and CD8 + during the disease course—went back up to the previous level after disease recovery (726 cells/µL)

chest CT-scan = bilateral ground-glass opacities

HTN

ESRD (on renal replacement therapy)

HIV (on ART)

–

Recovered (after 2-week hospitalization)

9

Geretti AM [39]

N = 47,592 COVID-19 patients N = 122 (0.26% with HIV-infection)

56 (49–62)

Male = 80 (66.1%)

–

HIV

Hemoglobin g/dL = 13.0

Anemia = 39 (36.5%)

WBC cells/µL = 6.6

Lymphocyte cells/µL = 1000

Lymphopenia (47.2%)

Platelet’s count/ µL = 197

Thrombocytopenia (24.8%)

PT sec = 13.6

Cr µmol/L = 89

GFR ml/min = 75

ALT U/L = 28

ALT > 40 U/L = (31.5%)

Glucose mmol/L = 6.8

Hyperglycemia (20.4%)

CRP mg/L = 107

Symptom duration (day) = 5

Current or former Smoker (30.9%)

Previous comorbidity (74.6%)

Chronic respiratory disease (10.8%)

Asthma (10.3%)

Cardiovascular disease (17.1%)

dementia (2.5%)

Diabetes mellitus, no complications (13.7%)

Diabetes mellitus, with complications (7.7%)

malignancy (3.4%)

Hematological disease (3.4%)

Obesity (17%)

chronic Renal failure (14.1%)

chronic neurological disorder (6.9%)

liver disease (7.6%)

HIV infection does not increase admission to critical care

HIV infection increases the risk of COVID-19’s mortality

In young patients, higher mortality was observed among HIV-infected cases (21.3%)

Adjusted hazard ratio = 2.87

26.7%

10

Gervasoni C [33]

N = 47 Co-infection HIV and COVID-19

51 (± 11)

Male = 36 (77%),

–

HIV

CD4 + cells/µL = 636 (± 290)

HIV viral load < 20 copies/ml = 44 (94%)

Disease duration (day) = 14

COVID-19 diagnosis: laboratory confirmed (60%), clinically suspected (50.8%)

Hospital admission: 13 (28%)

Pneumonia 12(25%)

Previous comorbidity (64%)

Dyslipidemia (31.9%)

Hypertension (29.8%)

Hepatitis C or B co-infection (10.64%)

renal disease (8.5%)

Diabetes mellitus (6.4%)

epilepsy (2%)

cardiovascular disease (4.3%)

malignancy (6.4%)

gastritis (4.3%)

organ transplant (2.1%)

Chronic respiratory disease (4.3%)

HIV-infected patients with COVID-19 are at the same risk of severe disease or death as the normal population

4.26%

11

Hadi YB [29]

N = 50,167 COVID-19 patients (HIV-infected = 404)

48.2 (SD 14.2)

Male = 285 (71%)

–

HIV

CRP mg/L = 71.15

LDH U/L = 372.45 (SD = 291.05)

ESR = 52.89

ALT U/L = 37.2

AST U/L = 48.43

Bilirubin mg/L = 0.84

Ferritin ng/mL = 23,646.94

ICU admission = 27 (6.7%)

Current or former Smoker (13.86%)

Hypertension (46.29%)

Chronic respiratory disease (25%)

Diabetes mellitus (22.03%)

Chronic kidney disease (16.58%)

in unmatched analysis: HIV-infected patients showed higher mortality (risk ratio 1.55) and higher inpatient service need (RR = 1.83)

After propensity score matching: no difference in mortality rate, but still higher inpatient service needs in HIV-infected patients

4.95%

12

Härter G [34]

N = 33 Co-infection HIV and COVID-19

48 (range 26–82 years)

Male = 30 (90.9%)

–

HIV

Median CD4 + T-cell = 670 cells/µL

HIV RNA < 50 copies/ml = 30 (93.75%)

Mild symptoms (76%)

severe (6%)

critical (18%)

requiring mechanical ventilation = 2 (6.1%)

ICU admission = 6 (18.2%)

Hospital admission (42%)

Previous comorbidity (60.0%)

Hypertension (30.3%)

Chronic respiratory disease (18.2%)

diabetes mellitus (12.1%)

cardiovascular disease (9.1%)

chronic Renal failure (6.1%)

Hepatitis B Co-infection history (15.2)

No increased morbidity and mortality among symptomatic COVID-19 co-infection with HIV on ART

9%

13

Ho H-e [30]

N = 93 Co-infection HIV and COVID-19

58 (52–65)

Male = 67 (72%)

–

HIV

during COVID-19 illness:

significant lymphopenia and decreased CD4 + T-cell counts and percentages

Nadir CD4 + , cells/µL = 220

CD4% = 23

HIV RNA < 50 copies/ml (89.1%)

Nadir WBC, cells/µL = 5100

Nadir ALC, cells/µL = 900

Nadir ANC, cells/µL = 3500

ALT U/L = 45

AST U/L = 61

Total bilirubin, mg/dL = 0.7

ALP, U/L = 96

Increased levels of inflammatory markers:

CRP, mg/L = 137.0

Fibrinogen, mg/dL = 626

D-dimer, μg/mL = 2.6

IL-6, pg/mL = 57.6

IL-8, pg/mL = 42.2

TNF-α, pg/mL = 21.8

IL-1β, pg/mL = 0.3

Hospital admission (77.4%)

ICU admission (20.4%)

mechanical ventilation = 15 (16.1%)

Current or former Smoker (54.8%)

Autoimmune disease (4.3%)

Cancer (8.6%)

Diabetes mellitus (34.4%) cardiovascular disease (18.3%) Hypertension (52.7%)

Chronic respiratory disease (26.9%) chronic kidney disease (17.2%)

ESRD (7.5%)

organ transplant (5.4%)

History of opportunistic infection (24.7%)

Died patients has significant lower nadir absolute lymphocyte count and higher level of Inflammatory markers

patients with HIV infection are at risk for severe COVID-19, especially with increased inflammatory markers and immune dysregulation having a worse prognosis

19 out of 93 (20.4%)

19 out of 72 hospitalized individuals (26.4%)

14

Karmen-Tuohy S [27]

N = 63 patients hospitalized with COVID-19 (HIV-positive N = 21 and matched non-HIV: N = 42)

–

–

–

HIV

On admission:

WBC = 7200

Hemoglobin = 12.70

Absolute neutrophil count = 5800

Absolute lymphocyte count = 1090 (higher in HIV positives)

Ferritin = 679

D-dimer = 333

Troponin = 0.02

Creatine phosphokinase = 239

Procalcitonin = 0.2

Creatinine = 1.14

CRP = 154.5 (higher in HIV positives)

LDH = 449.4

absolute CD4 count = 298

CD4 count < 200/mL (31.6%)

CD4% = 24

viral load < 50 copies/mL (88.2%)

Length of hospital stay, d = 6

ICU admission = 6 (28.6%)

mechanical ventilation = 5 (23.8%)

Abnormal initial chest X-ray 19 (90.5%)—(higher in HIV-positive patients)—no difference for abnormal chest X-ray ever-present during this hospitalization

Complications:

Myocardial infarction = 1 (4.8%)

Pulmonary embolism = 1 (4.8%)

Deep vein thrombosis = 1 (4.8%)

bacterial pneumonia = 3 (14.3%)

–

No difference in length of the hospital stays, rates of ICU admission, mechanical ventilation, and mortality

28.6%

15

N.S.C. van Oers [23]

An infant with X-SCID

Infant

Male

X-SCID

–

–

hepatitis

X-SCID

He received a haploidentical CD34 selected stem cell transplant

0%

16

Douglas Tremblay[40]

24 cancer patients treated with convalescent plasma for severe COVID‐19

69

58.3%male

–

Cancer

Hematologic malignancy (58%)

Solid malignancy (42%)

Neutropenic (0%)

Lymphocytopenic (58.3%)

95.9% required supplemental oxygen

16.7% require NIPPV

12.5% were intubated

HTN 62%

DM 33%

CKD 29%

CAD 20%

COPD 20%

CHF

Obesity 20%

–

41.7%

17

K. Sigel [35]

88 PLWH hospitalized with COVID-19

61

75%male

–

HIV

WBC = 7.2

Creatinine = 1.2

D-dimer = 1.98

CRP = 119

Ferritin = 692

IL6 = 64.1

Prolactin = 0.21

LDH = 428

Moderate/Severe 17%

Severe 21%

DM 27%

HTN38%

Obesity 10%

Cirrhosis 6%

COPD 9%

CAD 7%

CKD 22%

Organ transplant 5%

Cancer 17%

no differences in adverse outcomes associated with HIV infection for hospitalized COVID-19 patients compared with a similar comparison group

21%

18

A. M. Shields [21]

100 patients with PID and symptomatic SID

PID: 30

SID: 15

44%male

N = 60 (CVID

Undefined primary antibody deficiency

XLA)

N = 40 (Chronic lung, Cardiovascular, Chronic liver disease, Diabetes mellitus)

–

–

–

Patients with PID and symptomatic SID showed a higher risk of morbidity and mortality from COVID-19

Infection–fatality ratio

PID: 20%

SID: 33%

19

N. Shalev [36]

31PLWH Hospitalized for Coronavirus

60.7

Male 77%

–

HIV

Lymphocyte = 12.6

CRP = 182

Ferritin = 1356

d-dimer = 6.9

Procalcitonin = 2.2

Low-flow nasal cannula 42%

Non-rebreather mask 23%

Mechanical ventilation 26%

Fever 74%

Radiologic changes 65%

HTN67%

DM 42%

CKD 23%

COPD 26%

Obesity 33%

Clinical outcomes were comparable to patients who investigated in other hospitalized cohorts

25.8%

20

S. R. Nagarakanti [37]

23 HIV patients admitted for COVID‐19

59

Male 51%

–

HIV

WBC = 6.6

Lymphocytes = 16%

HGB = 13

PLT = 310

D-dimer = 193

Albumin = 2.1

Procalcitonin = 3.1

CPK = .025

LDH = 240

required ICU admission 9%

HR > 100 52%

RR > 20 83%

Ambient air 74%

Nasal Cannula 9%

NRB 13%

HFNC 4%

HTN 65%

CKD 48%

DM 30%

CAD 9%

COPD 4%

Compare to the matched controls, no difference in mortality and critical care needs for HIV patients

13%

21

H. Miyashita [31]

161 HIV patients with COVID-19

60

–

–

HIV

–

ICU admission 22%

Intubation 12%

HTN 46%

DM 29%

CKD 24%

Dyslipidemia 34%

HF 9%

Young COVID‐19 patients with HIV infection are at a higher risk for mortality and invasive intubation, compared with non-HIV patients

14%

22

I. Meyts [26]

94 patients with IEI with SARS-CoV-2 infection

30

65%male

Primary antibody deficiency (56%)

immune dysregulation syndrome (9.6%)

phagocyte defect (6.4%)

autoinflammatory disorder (7.4%)

combined immunodeficiency (15%)

innate immune defect (3%)

bone marrow failure (2%)

–

–

ICU admission 20%

Asymptomatic 11%

Mild 25%

Hospitalization 63%

–

Patients with IEI mainly experience a mild form of the disease

same risk factors predict severe disease of IEI and normal population

9.5%