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Original Clinical Science—General

Coronavirus Disease-19: Disease Severity and Outcomes of Solid Organ Transplant Recipients: Different Spectrums of Disease in Different Populations?

Ali, Tariq MD1; Al-Ali, Ali MD1; Fajji, Layal BSN1; Hammad, Ehab MD1; Nazmi, Ahmed MD1; Alahmadi, Ibrahim MBBS1; Aleid, Hassan MD1; Ullah, Asad MD1; Shah, Yaser FRCP1; Broering, Dieter PhD1

Author Information
doi: 10.1097/TP.0000000000003433
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Abstract

INTRODUCTION

The novel coronavirus disease-19 (COVID-19) has swept through the world and affected millions of people. A pandemic of significant mortality, the elderly, patients with comorbid conditions, and the immunocompromised are especially at risk.1 Viral diseases, especially respiratory viral infections, are common in solid organ transplant (SOT) recipients, as their immune systems are suppressed due to immunosuppressive medications.2,3

An early report from New York City showed alarming outcomes of kidney transplant recipients diagnosed with COVID-19.4 The mortality rate was 28% in these patients, which increased to 64% if they were intubated. A smaller study of 10 patients from the United States reported a mortality of 30% in kidney transplant recipients.5 A case series from the Columbia University transplant program reported favorable outcomes for kidney transplant recipients when using a Hydroxychloroquine and Azithromycin combination, in addition to holding antimetabolites.6 A systemic review reported a fatality rate of around 38% in liver transplant recipients and 17% among kidney transplant recipients.7 A further study investigated outcomes of SOT patients including liver, lung, and kidney transplant recipients.8 Researchers reported a mortality of 24% in hospitalized patients, which increased to 52% in patients who were admitted to the intensive care unit (ICU). Similarly, significant mortality was observed among SOT recipients in a study from the Netherlands.9 Indeed, all early studies have shown that the mortality was significantly higher in SOT recipients.

Saudi Arabia has a population of approximately 34 million. Healthcare is completely free for all citizens and is fully subsidized by the government. Moreover, the government allocates health budgets to hospitals to meet healthcare costs. Patients are also reimbursed for the traveling costs of follow-up visits. The first case of COVID-19 was reported in Saudi Arabia on March 2, 2020, while the first kidney transplant patient was diagnosed with COVID-19 on March 23. Based on the aforementioned studies, we expected a rise in the number of cases among all SOT recipients. However, we neither saw a rapid case increase nor observed any mortality in the initial phase of the disease. Furthermore, the government took various initiatives to curb the spread of the disease. This included a full-time, countrywide curfew implemented from March 23. During this period, however, people were allowed to do essential jobs and go for grocery shopping in the specified local areas. The curfew restrictions were gradually eased from May 28 and completely removed on June 20.

We are the largest SOT program in the region and performed 239 kidney transplants, 186 liver transplants, and 38 lung transplants last year. SOT recipients receive continued follow-up in our hospital and this monitoring is life-long. Currently, we have around 3000 SOT recipients under regular follow-up. Yet, as reports of high incidence and mortality emerged internationally, we had very few cases of COVID-19 among our SOT recipients. This study aimed to determine the outcomes of the SOT recipients who were under our long-term follow-up and were diagnosed with COVID-19. The outcomes studied were development of severe disease, ICU admission, and mortality.

MATERIALS AND METHODS

This study included all SOT patients under our long-term follow-up who were diagnosed with COVID-19, whether in our hospital or elsewhere. If patients were diagnosed in their local area, we were notified by the individuals themselves or by the hospital. Notably, we established a system to make regular contact with the patients, either through phone clinics or during the medication refill process. Moreover, a special COVID-19 team was established to contact and monitor the patients regardless of whether they were admitted to our hospital.

We recorded patients’ demographic details and noted whether they were admitted or being managed at home. We also recorded patients’ COVID-19 stage, the medications used to treat them, any ICU admissions, as well as graft and patient survival.

Diagnosis

Patients were diagnosed with COVID-19 if severe acute respiratory syndrome coronavirus (SARS-CoV-2) RNA was detected on nasopharyngeal swabs. A real-time reverse transcription polymerase chain reaction (PCR) assay was used to detect the SARS-CoV-2 RNA. Patients were tested for SARS-CoV-2 PCR if they presented with symptoms suggestive of COVID-19. Asymptomatic patients were tested if they had a history of contact with a confirmed case of COVID-19, before undergoing a procedure or before admission to the hospital for any reason.

Disease Severity

To determine the disease severity, patients were assigned to one of the following stages, per the institution’s COVID-19 guidelines.

Asymptomatic (Stage A)

Patients with no signs or symptoms of infection.

Mild Infection (Stage B)

Patients with upper respiratory tract infection symptoms and other mild symptoms (including fever and gastrointestinal symptoms) but without evidence of pneumonia.

Moderate Infection (Stage C)

Patients with hypoxia with oxygen saturation <93% at rest, or the presence of pneumonia not requiring ICU admission.

Severe Infection (Stage D)

Patients with pneumonia requiring ICU admission, or any of the following:

  1. Respiratory rate of ≥30 breaths/min.
  2. Arterial oxygen partial pressure to fractional inspiratory oxygen ratio (PaO2/FiO2) <300.
  3. More than 50% lung involvement on imaging within 24–48 hours.
  4. Critical respiratory failure requiring mechanical ventilation, septic shock, or multiorgan dysfunction.

Treatment Strategies

Stage A

No specific treatment, only supportive care and infection control measures.

Stage B

Hydroxychloroquine ± Azithromycin for 5 days.

Stage C

Hydroxychloroquine ± Azithromycin for 5 days.

Intravenous antibiotics for suspected bacterial infection.

Tocilizumab for worsening condition (after discussion with the infectious diseases team).

Consider lopinavir/ritonavir or chloroquine for 6–10 days.

Dexamethasone for worsening respiratory signs/symptoms.

Stage D

The same as stage C, with the addition of Dexamethasone for all patients

Medication Dosing Protocol

Azithromycin was given in a loading dose of 500 mg, followed by 4 further doses of 250 mg daily. Hydroxychloroquine was administered in a dose of 400 mg, twice daily, for 1 day—then continued in a dose of 200 mg, twice daily, for further 4 days. Patients were frequently monitored by serial electrocardiograms for QTc prolongation.

Tocilizumab was used if there was evidence of cytokine storm. H score was used to determine the hyperinflammation state.10 An initial dose of 400 mg was given upon the diagnosis of cytokine storm and, if no response was observed within 12 hours, a second dose was administered.

Dexamethasone was a new addition to the treatment. An initial dose of 6 mg daily was given and the dose was escalated if required.

Immunosuppression Management

With the exception of steroids and Tacrolimus, other immunosuppressive medications including antimetabolites were stopped. The dose of steroids was increased or intravenous hydrocortisone was administered in patients with moderate to severe disease.

Statistical Analysis

Data are expressed as frequencies (percentages), mean scores (SD), and median (ranges) where applicable. Chi-square or Fisher’s exact tests were used to compare categorical variables. Student’s t-test was used to compare the mean scores of the 2 groups and Kruskal-Wallis test was used to compare median values in the COVID-19 stages. A value of P < 0.05 was considered to be significant.

Ethical Approval

This study was classified as noninterventional study by the hospital’s research department and was approved by the department’s research subcommittee. A written consent is also obtained for all SOT to use their clinical and laboratory data for registry as well as for the research purpose.

RESULTS

Demographic Data

Approximately 3052 SOT patients are under our care. A total of 2266 kidney transplant recipients, 633 liver transplant recipients, and 153 lung transplant recipients are currently being followed in our center. To our knowledge, 360 patients (11.8%) were tested for COVID-19 and to date, 67 tested positive. Hence, 18.6% of the tested patients were positive for COVID-19.

As some patients were tested more than once, a total of 549 tests were performed. The reasons for testing included symptoms suspicious for COVID-19 (43%), screening before a surgical or radiological procedure (42%), screening before hospital admissions for reasons other than COVID-19 (11%), and screening due to contact with a confirmed case of COVID-19 (4%).

A total of 67 SOT recipients were diagnosed with COVID-19 (Table 1). Of these, 44 were kidney transplant recipients, 15 were liver transplant recipients, and 8 were lung transplant recipients. The majority (69%) were male. Liver transplant patients were older (mean age: 63 y) than kidney transplant recipients (50 y) and lung transplant recipients (44 y). Ten of the 67 individuals (5 kidney recipients, 4 liver recipients, and 1 lung recipient) had received their transplant within the past year.

TABLE 1. - Patients’ characteristics and demographic data
All Kidney Liver Lung
Total 67 44 15 8
Donor type (%)
 Living donor 45 (67.2) 37 (84.1) 8 (53.3) 0 (0.0)
 Deceased donor 22 (32.8) 7 (15.9) 7 (46.7) 8 (100)
Age
 Mean (SD) 51.8 (16.1) 49.6 (15.3) 62.7 (14.9) 43.5 (13.8)
 <50 y (%) 25 (37.3) 19 (43.2) 2 (13.3) 4 (50.0)
 ≥50 y (%) 42 (62.7) 25 (56.8) 13 (86.7) 4 (50.0)
Male gender (%) 46 (68.7) 29 (65.9) 11 (73.3) 6(75.0)
Time since transplant
 Years, median (range) 5.1 (0.1–17.4) 5.8 (0.2–17.4) 5.1 (0.1–14.5) 3.9 (0.7–9.3)
 <1 y (%) 10 (14.9) 5 (11.4) 4 (26.7) 1 (12.5)
 >1 y (%) 57 (85.1) 39 (88.6) 11 (73.3) 7 (87.5)
Comorbidity (%)
 Diabetes 29 (43.3) 17 (38.6) 10 (66.7) 2 (25.0)
 Hypertension 23 (34.3) 21 (47.7) 2 (13.3) 0 (0.0)
 Ischemic heart disease 10 (14.9) 7 (15.9) 1 (6.7) 2 (25.0)
Immunosuppression (%)
 Prednisone 57 (85.1) 44 (100) 5 (33.3) 8 (100)
 Tacrolimus 65 (97.0) 43 (97.7) 14 (93.3) 8 (100)
 MMF/Aza 58 (86.6) 43 (97.7) 9 (60.0) 6 (75.0)
Stage (%)
 A 17 (25.4) 13 (29.5) 4 (26.7) 0 (0.0)
 B 19 (28.4) 13 (29.5) 3 (20.0) 3 (37.5)
 C 23 (34.3) 13 (29.5) 6 (40.0) 4 (50.0)
 D 8 (11.9) 5 (11.4) 2 (13.3) 1 (12.5)
Labs, median (range)
 Ferritina 393 (7–3946) 899 (9–3946) 322 (121–1486) 216 (7–1206)
 Lactic dehydrogenaseb 309 (150–868) 298 (150–868) 359 (210–489) 352 (199–635)
 C-reactive proteinc 63 (0.2–300) 51 (0.5–300) 117 (6–168) 11 (0.2–286)
 D-dimerd 0.64 (0.27–6.7) 0.55 (0.27–6.7) 1.23 (0.42–5.8) 0.67 (0.31–5.66)
Chest X-ray film (%)
 Positive 29 (43.3) 18 (40.9) 7 (46.7) 4 (50.0)
 Negative 18 (26.9) 13 (29.5) 3 (20.0) 2 (25.0)
 Not done 20 (29.8) 13 (29.5) 5 (33.3) 2 (25.0)
Chest CT (%)
 Positive 17 (25.4) 10 (22.7) 2 (13.3) 5 (62.2)
 Negative 5 (7.5) 2 (4.5) 2 (13.3) 1 (12.6)
 Not done 45 (67.1) 32 (72.7) 11 (73.3) 2 (25.0)
CT, computed tomography; MMF/Aza, Mycophenolate Mofetil/Azathioprine.
aFerritin (normal range, 30–400 μg/L).
bLactic dehydrogenase (normal range, 135–225 units/L).
cC-reactive protein (normal range, <3 mg/L).
dD-dimer (normal range, 0.0–0.50 μg/mL).

At the time of the COVID-19 diagnosis, most SOT recipients were taking Prednisone (85%), Tacrolimus (97%), and antimetabolites (87%). The most common antimetabolite was Mycophenolate Mofetil; only 2 patients were taking Azathioprine.

Presenting Symptoms

A total of 17 patients were asymptomatic. The most common presenting symptoms were fever (80%), cough (60%), breathlessness (24%), sore throat (24%), diarrhea (19%), and anosmia (16%). Nearly half (42%) had a history of contact with someone who had tested positive for COVID-19 (usually a close relative).

Radiological Investigations

Chest radiographs were performed in 47 (70%) patients. Approximately 41% of the kidney transplant patients, 47% of the liver transplant patients, and 50% of the lung transplant patients had abnormal chest X-ray films consistent with the diagnosis of COVID-19 pneumonia (Table 1). The corresponding values for abnormal computed tomography (CT) scans were 23%, 13%, and 62%, respectively. In the initial phase of the pandemic, CT scans were conducted for all symptomatic patients and those with radiograph abnormalities. Later, CT scans were performed only if there was a clinical indication.

Factors Associated with Disease Severity

There were 17 (25%) patients in stage A, 19 (28%) in stage B, 23 (34%) in stage C, and 8 (12%) in stage D (Table 2).

TABLE 2. - Stages and factors associated with disease severity
A B C D P
Total 17 19 23 8
Agea 53 (19–69) 42 (25–76) 57 (26–78) 63 (30–75) 0.09
Maleb 13 (76.5) 12 (63.2) 15 (65.2) 6 (75.0) 1.00
Femaleb 4 (23.5) 7 (36.8) 8 (34.8) 2 (25.0)
Lab datab
 Ferritin NAc 173 (9–1858)d 684 (7–2644) 980 (199–3946) 0.06
 LD NAc 224 (150–383)e 338 (210–635) 546 (384–868) <0.01
 CRP NAc 8 (3–230)f 94 (0.2–300) 103 (4–300) 0.05
 D-dimer NAc 0.42 (0.27–0.96)g 0.78 (0.31–5.80) 3.14 (1.23–6.7) <0.01
aMedian (range).
bNumbers (%).
cNo data as usually patients were not admitted.
dFerritin (normal range, 30–400 μg/L).
eLactic dehydrogenase (normal range, 135–225 units/L).
fC-reactive protein (normal range, <3 mg/L).
gD-dimer (normal range, 0.0–0.50 μg/mL).
CRP, C-reactive protein; LD, lactic dehydrogenase.

Age

The median ages of the patients were as follows: 53 years in stage A, 42 years in stage B, 57 years in stage C, and 63 years in stage D. Although patients’ median age was higher in stages C and D, there was no significant difference across the stages (P = 0.09). However, when patients in stages C and D together are regarded in conjunction, they were significantly older than those in stage A (P = 0.04) and stage B (P = 0.03).

Gender

There was no difference in gender and disease severity (P = 1.00) across the stages.

Laboratory Data

There was an increasing trend of higher ferritin levels across the stages, but this was not statistically significant (P = 0.06). Similarly, C-reactive protein (CRP) was higher across the stages, but this trend was not statistically significant (P = 0.05). The lactic dehydrogenase (LD) levels and D-dimer levels were significantly higher across the stages (P < 0.01) (Table 2).

Clinical Course, Management, and Outcomes

A total of 47 patients (70%) with COVID-19 were admitted to the hospital. Around 71% of kidney transplant recipients, 67% of liver transplant recipients, and 75% of lung transplant recipients who were diagnosed with COVID-19 were admitted. The remaining patients were managed at home (Table 3).

TABLE 3. - Clinical course, management, and outcomes
All Kidney Liver Lung
Admitted/total (%) 47/67 (70.1) 31/44 (70.5) 10/15 (66.7) 6/8 (75.0)
Hospital days, median (range) 9 (1–42) 9 (1–42) 14 (4–16) 9 (9–13)
Follow-up days, median (range) 35 (9–126) 41 (11–126) 29 (9–63) 27 (17–63)
Supplementary oxygen
 None 26 (55.3) 19 (61.3) 5 (50.0) 2 (33.3)
 24%–28% 10 (21.3) 7 (22.6) 1 (10.0) 2 (33.3)
 >28% 7 (14.9) 2 (6.5) 4 (40.0) 1 (16.7)
 Noninvasive ventilation 2 (4.3) 2 (6.5) 0 (0.0) 0 (0.0)
 Mechanical ventilation 2 (4.3) 1 (3.2) 0 (0.0) 1 (16.7)
Acute kidney injury (%) 9 (19.1) 5 (16.1) 3 (30.0) 1 (16.7)
Treatment (%)
 Hydroxychloroquine 39 (82.9) 26 (83.9) 8 (80.0) 5 (83.3)
 Azithromycin 42 (89.4) 28 (90.3) 8 (80.0) 6 (100)
 Tocilizumab 11 (23.4) 5 (16.1) 3 (30.0) 3 (50.0)
 Dexamethasone 9 (19.1) 4 (12.9) 3 (20.0) 2 (33.3)
Intensive care admission (%) 10 (14.9) 5 (16.1) 4 (40.0) 1 (16.7)
Graft loss (%) 2 (4.3) 2 (6.5) 0 (0.0) 0 (0.0)
Death (%) 2 (4.3) 1 (3.2) 0 (0.0) 1 (16.7)

Length of Stay and Disease Duration

The median length of stay was 9 days. Liver transplant recipients stayed longer (median stay: 14 d) than the other SOT recipients (Table 3). All patients have been discharged from the hospital. To date, the median follow-up since a positive nasopharyngeal swab is 35 days (Table 3).

Respiratory Support

Approximately 45% of admitted patients required supplementary oxygen. Two patients required noninvasive ventilation and another 2 required mechanical ventilation.

Acute Kidney Injury

Acute kidney injury (AKI) was defined per the acute kidney injury network (AKIN) criteria.11 A total of 9 (13%) patients developed AKI: 16% of kidney transplant recipients, 30% of liver transplant recipients, and 17% of lung transplant recipients developed AKI. Of these nine, 3 were in the AKIN-1 category, 2 were in AKIN-2, and 4 were in AKIN-3. Two of the AKIN-3 patients had advanced graft dysfunction before this illness and began dialysis during this admission. One patient in AKIN-3 has recovered while the fourth patient who required dialysis has died.

Pharmacological Interventions

Almost all patients continued to receive Prednisone and Tacrolimus; however, the antimetabolites were stopped.

Most symptomatic patients received a Hydroxychloroquine and Azithromycin combination. Approximately 16% of kidney transplant recipients, 30% of liver transplant recipients, and 50% of lung transplant recipients received Tocilizumab (Table 3). Of those who required Tocilizumab, 8 were in stage D and 3 in stage C. Nine of these patients have been discharged from the hospital and 2 have died.

ICU Admission

Ten patients were admitted to the ICU; this number comprised of 16% kidney transplant recipients, 40% liver transplant recipients, and 17% lung transplant recipients. One lung transplant recipient and 1 kidney transplant recipient required mechanical ventilation and both have died. Other patients have been discharged from the hospital.

Patient and Graft Survival

One lung transplant recipient and 1 kidney transplant patient have died. Both were managed in the ICU and required mechanical ventilation.

Two kidney transplant patients lost their grafts. Notably, however, both these patients had advanced graft dysfunction before this illness. One patient had a baseline serum creatinine of 427 μmol/L (4.8 mg/dL), while the other patient’s serum creatinine was 447 μmol/L (5.4 mg/dL) before COVID-19.

DISCUSSION

A previously stated, the incidence of severe disease in the region of this study is low, particularly in comparison with the published data from the West. Although 2 patients have died, the outcomes of our SOT recipients are quite favorable.

Saudi Arabia diagnosed its first case of COVID-19 on March 2, 2020. By the end of March, this number increased to around 150 cases per day.12 A curfew was imposed on the 23rd of the same month—but cases continued to increase. By mid-May, nearly 3000 cases were being recorded per day. The curfew was relaxed from May 28, and the number of daily cases peaked at almost 5000 on June 16. This number gradually dropped, and approximately 2500 cases were recorded on July 21. Currently, there are around 256 000 confirmed national cases and 2500 deaths (73 deaths pmp).13 The case-fatality ratio in Saudi Arabia is also low, at 1%, compared with 3.6% in the United States and 15.3% in the United Kingdom.14 Our country ranks at number 20 in terms of global case-fatality ratio.

Saudi Arabia has a population of over 34 million, and around 277 000 individuals tested positive (0.8%) for COVID-19.13 In our facility, 67 of approximately 3000 SOT recipients tested positive for the virus (2.2%). Thus, the percentage of SOT patients who tested positive was significantly higher in our hospital than that of the general population.

In the whole country, around 3 million tests have been performed. Among those who were tested for COVID-19, 9.2% were diagnosed with COVID-19. In our hospital, around 7% of the tested patients (non-SOT) were positive for COVID-19 PCR. In comparison, the positive rate among SOT recipients was significantly higher at 18.6%. Notably, however, the ICU admission rates and mortality rates of our SOT recipients were low in comparison with those reported in data from Western countries.

In the United States, the initial reports from New York showed significantly greater mortality among transplant recipients.4-6 Indeed, a study published in the New England Journal of Medicine reported 28% mortality in the kidney transplant recipients. This study, from the Montefiore Medical Center, included patients who were diagnosed between March 16 and April 1. It is worth noting that New York’s first diagnosis of COVID-19 took place on March 1 and the city quickly became the epicenter of the disease. Moreover, New York reached a total mortality of 25% in all COVID-19-related deaths during the month of March.6 Thus, it appears that COVID-19 mortality rates were very high in the early phase of disease, when it was spreading rapidly.

Conversely, in Saudi Arabia, the disease spread was quite slow, and the initial phase was marked by lower mortality rates. Thus, it is plausible that early measures worked to prevent a rapid case increase. This may have contributed to low mortality in our cohort, as well as in the rest of the population. A previous study used a mathematical model to investigate the effectiveness of social distancing in reducing the spread of the disease.15 The author concluded that this intervention averted new cases, hospitalization and death.15 However, when the intervention ended, the epidemic rebounded. We carried out a survey of around 1500 SOT recipients (results not shown) between April and June 2020. Results demonstrated that around 50% of the patients stayed at home, another 40% went out infrequently, and <10% went out frequently. Such behavior would certainly have helped stem the spread of the disease among our patients.

Another potential factor which could be associated with a low incidence of severe disease is previous exposure to Middle East Respiratory Syndrome Coronavirus. This disease was mainly concentrated in the Arabian Peninsula, but most of the cases occurred in Saudi Arabia.16 A pilot serological study showed possible crossreactivity for common coronavirus antibodies for COVID-19–related antigens.17 The authors hypothesized that children’s low COVID-19 incidence may be due to previous exposure to a coronavirus that was more closely related to COVID-19.16 However, a significant number of people would have had to be exposed to Middle East Respiratory Syndrome Coronavirus to achieve this benefit. This may be an interesting avenue for future research.

Most of our symptomatic patients were treated with a Hydroxychloroquine and Azithromycin combination. On one hand, Azithromycin has been shown to have antirhinovirus activity in the bronchial epithelial cells.18 Its antiviral activity and immunomodulatory effects may be beneficial in COVID-19 patients.19 Notably, however, an article has criticized its role in treating COVID-19.20 On the other hand, Hydroxychloroquine suppresses tumor necrosis factor α and interleukin-6 (IL-6), which may help to prevent lung injury in viral-associated pneumonia.19

Previous studies support the idea that coronaviridae infect their target cells through an endocytic pathway and that chloroquine might inhibit their replication.19,21,22 A study that demonstrated the negative impact of Hydroxychloroquine in treating COVID-19 was later retracted by the Lancet, due to inaccuracies in the data.23 A statement issued by the “RECOVERY Trial” team stated, however, that there was no beneficial effect of Hydroxychloroquine use in patients hospitalized with COVID-19.24 As we have not observed any significant problems in using the Hydroxychloroquine/Azithromycin combination—and the outcomes are generally favorable (which is likely to be multifactorial)—this combination remains a part of our treatment protocol.

SARS-CoV has been described as having powerful immunostimulatory activities to induce considerable proinflammatory cytokine release (eg, tumor necrosis factor α, IL-6, and interleukin-12).25 As Tocilizumab, a monoclonal antibody, targets the IL-6 pathways, it has a potential role in the treatment of COVID-19.26 Accordingly, a study from China reported excellent treatment outcomes for COVID-19-related severe disease.27 We have treated 11 patients with Tocilizumab; 2 patients have died and others have responded well to this treatment in combination with others.

As reported in other studies, we discontinued the use of antimetabolites.8,9 However, steroids and Tacrolimus were continued. A review article observed that some viruses use the active immunophilin pathway for their life cycles, which is blocked by calcineurin inhibitors. Thus, blocking this pathway may reduce the viral replication.28 The article contends that calcineurin inhibitors reduce cytokine release and this may actually be beneficial in preventing cytokine storm associated with COVID-19.28

In the present study, certain factors were associated with progressive stages of disease severity. Age, ferritin level, LD level, D-dimer, and CRP levels showed increasing trends as the stage worsened. When we analyzed the cohort by combining stage C and stage D patients, they were significantly older than patients in stage A and stage B. Yet, only LD levels and D-dimer levels were significantly associated with worsening stage. A previous study showed that although the median CRP level was within normal range, 46% of the patients had elevated CRP levels.4 Another study showed increased ferritin, CRP, and D-dimer levels but no difference was observed between mild and moderate/severe disease.8

In the present study, 5 kidney transplant recipients, 4 liver transplant recipients, and 1 lung transplant recipient underwent their transplants in the past year. The total numbers of each transplant type performed in the last year were 239, 186, and 38, respectively. Ultimately, the incidence of COVID-19 diagnosis was around 2% in recent SOT recipients. Thus, despite receiving high immunosuppression, this demographic’s risk of developing severe disease was low.

It must be noted that this study has some limitations. The number of patients with COVID-19 diagnosis is relatively small. This is, however, comparable to some of the previous studies. Although the first case in Saudi Arabia was reported in March, the disease peaked in mid-June, hence, the worst may be yet to come. While this is possible, most reports showed the worst outcomes at the start of the disease. Another limitation is the small number of patients, which prevented us from performing advanced statistical analyses. Finally, though all the positive results were relayed to us, the negative tests from local hospitals were not. Hence, it is likely that negative tests are underreported in this study.

At this stage, we do not know for certain why our patients’ mortality is low. It might be that the outcomes are determined by the associated comorbid conditions, and other factors, not only the immunosuppressive state. Moreover, the disease patterns may differ among populations, and the virulence of COVID-19 in this study’s region may differ also. However, 2 distinct features in our patients were partial-to-full social isolation (due to curfew), and personal response to the pandemic. This might have helped to slow the spread of the disease, which might have resulted in lower mortality. It is also possible that since we experienced a peak at a later time, we learned from the experience of the rest of the world and had time to develop strategies and treatment protocols. Our results should be interpreted with caution, as the pandemic continues and outcomes may change in future. In our experience, early and aggressive social isolation policies, as well as pharmacological interventions may be associated with better outcomes.

In conclusion, our study demonstrates that most patients at our center had mild to moderate disease. Moreover, few required ICU admission and the overwhelming majority have recovered. To date, 2 patients have died and the remaining patients have been discharged from the hospital.

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