COVID-19

 

Doctors who treat it with Ivermectin

FLCCC Doctors: I created a document based on the FLCCC's list of doctors, which I update on who treats people who are immunocompromised, whether on chemotherapy or who have had an organ transplant. You can view that here; you may have to request permission to access it. You can also view the list on FLCCC's website directly here

Kidney Transplant Recipients

 

Outcomes of critically ill solid organ transplant patients with COVID-19 in the United States

Death within 28 days of ICU admission was similar in SOT and non-SOT patients (40% and 43%, respectively; relative risk [RR] 0.92; 95% confidence interval [CI]: 0.70-1.22).

There was a trend toward higher risk of acute kidney injury requiring renal replacement therapy in SOT vs. non-SOT patients (37% vs. 27%; RR [95% CI]: 1.34 [0.97-1.85]). Death and organ support requirement were similar between SOT and non-SOT critically ill patients with COVID-19.

COVID-19 mortality among kidney transplant candidates is strongly associated with social determinants of health

384 denoted a COVID-19 cause (5.00/1000 person years)

Factors associated with increased COVID-19 mortality included increased age, males, higher body mass index, and diabetes. In addition, Blacks (IRR = 1.96, 95% C.I.: 1.43-2.69) and Hispanics (IRR = 3.38, 95% C.I.: 2.46-4.66) had higher COVID-19 mortality relative to Whites. Patients with lower educational attainment, high school or less (IRR = 1.93, 95% C.I.: 1.19-3.12, relative to post-graduate), Medicaid insurance (IRR = 1.73, 95% C.I.: 1.26-2.39, relative to private), residence in most distressed neighborhoods (fifth quintile IRR = 1.93, 95% C.I.: 1.28-2.90, relative to first quintile), and most urban and most rural had higher adjusted rates of COVID-19 mortality. Among kidney transplant candidates in the United States, social determinants of health in addition to demographic and clinical factors are significantly associated with COVID-19 mortality.

 

COVID-19 related mortality in kidney transplant and hemodialysis patients: a comparative, prospective registry based study

 

Death rates were relatively low, when you take into account the study above which states that social factors play a significant role in recovery.

 

"16.9% of kidney transplant and 23.9% of hemodialysis patients died within 28 days of presentation.

This risk was dramatically increased during the first post-transplant year. In-center hemodialysis are at higher risk for COVID-19 related mortality, independent from known risk factors such as obesity, ischemic heart disease and lung disease.2 Kidney transplant recipients also represent a vulnerable population for viral diseases because of their immunosuppressive agents and are at specifically high risk for COVID-19 related mortality.3 

 

Hemodialysis patients were more frequently diagnosed with COVID-19 as a result of a routine screening or because of a COVID-19 contact while being asymptomatic. Consequently, more kidney transplant recipients than hemodialysis patients presented with symptoms like cough, shortness of breath, headache, nausea or vomiting, diarrhea, myalgia or arthralgia, and fever. Although their O2 saturation at presentation was similar to those of hemodialysis patients, kidney transplant recipients had a higher temperature, respiration rate, pulse rate and C-reactive protein (CRP) levels. Kidney transplant recipients more often used RAAS inhibitors than hemodialysis patients and all of them were on immunosuppression (Table 1)."

Study - A family cluster of diagnosed coronavirus disease 2019 (COVID-19) kidney transplant recipient in Thailand

Our case series plausibly affirmed a person-to-person transmission and potentially severe disease in the transplant population. Clinicians who are encountering with transplant recipients should be aware of possible transmission among family members.

The clinical course of the disease seems to be mild in the majority especially those who are young and free of comorbidities. However, those who are elderly, occupied by chronic medical conditions, or immunocompromised tend to have more severe disease and mortality rates.

 

A 38‐year‐old man (a son of Case 1) who underwent a living‐related KT in 2014 who complained of fever and myalgia for 3 days before this admission. He had a history of travel to Bangkok for a follow‐up visit 1 week before this event. His allograft has been maintained on tacrolimus 2 mg/d, mycophenolate sodium 720 mg/d, and prednisolone 5 mg/d. Baseline creatinine and estimated glomerular filtration rate (eGFR) was 0.9 mg/dL and 70.7 mL/minute/1.73 m2, respectively. He also had chronic hepatitis B on lamivudine 150 mg/d.

A diagnosis of COVID‐19 was suspected based on a history of contact with a confirmed COVID‐19 case (a primary case).

 

 He was empirically treated with oral oseltamivir and oral cefixime while waiting for nasopharyngeal and throat swab for SARS‐Co‐V2 PCR and influenza antigen, which both later revealed negative. However, his fever had persisted until day 6 of admission without localizing symptoms or signs hence for a reassessment for SARS‐CoV‐2 PCR from nasopharyngeal and throat swab, which reported as positive. 

 

Hydroxychloroquine 800 mg/d, ritonavir‐boosted lopinavir 800 mg/d, azithromycin 250 mg/d, and favipiravir 1200 mg/d were initiated. Mycophenolate sodium was withdrawn, tacrolimus was decreased for low trough level and prednisolone was decreased to 15 mg/d. Intravenous ertapenem and levofloxacin were empirically started 2 days after clinical deteriorating. One week after treatment, he still had persistent fever, tachypnoea as well as new‐onset of diarrhea. 

The exam revealed respiratory rate of 28/minute with oxygen saturation 95% on oxygen 3 LPM. His labs included WBC 6200 cells/mm3, N 88%, creatinine 3.01 mg/dL, lactate dehydrogenase (LDH) 292 IU/mL, CRP 96.1 mg/L, ferritin 2790 ng/mL, and tacrolimus level 66.3 ng/mL.

 

His respiratory status has been deteriorating. He was supported by a high‐flow nasal cannula oxygen therapy then practical application of awakening prone ventilation for ARDS. Antibiotic was further escalated to intravenous meropenem for the assumption of secondary bacterial infection. Finally, his clinical and CXR had improved, medications were stopped after 10 days of treatment without adverse reaction. The PCR for SARS‐CoV‐2 from sputum turns to be negative after 20 days of treatment. Except for serum creatinine, which was increased to 2 mg/dL, the rest were decreased, including GFR 40.83 mL/minute/1.73m2, CRP 1.9 mf/L, LDH 142 IU/L, and serum ferritin 1459 ng/mL.

His hospitalization was complicated by Clostrioides difficile colitis requiring oral vancomycin and intravenous metronidazole.Although they did not live in the same household however, in the same neighborhood with frequent visits among each other. 

 

Chen et al 21 reported three closed family members, which included a KT recipient husband, his wife, and his son, who live in the same household contracting the disease from unknown sources during an outbreak in China.

 

Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients

In conclusion, the clinical features and management of two COVID‐19 cases in SOT recipients were reported above. From this experience, the regimen for COVID‐19 positive SOT recipients should be adjusted after comprehensive evaluation, according to the infection level, immunosuppressant concentration, immune status, and side effects. A therapeutic regimen consisting of reduction of calcineurin inhibitors and MMF, combined with low‐dose methylprednisolone, is recommended at present. Certainly, further data are needed to gain better understanding of the impact of immunosuppressive therapy on the clinical presentation, severity, and outcome of COVID‐19 in SOT recipients.

 

Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID-19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus-related hepatocellular carcinoma and was confirmed to have COVID-19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low-dose methylprednisolone-based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living-related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID-19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID-19. These effectively treated cases can provide a basis for immunosuppressant management of COVID-19-positive SOT recipients.

 

Case 1. These abnormalities suggested the possibility of COVID‐19 infection, so the patient was immediately transferred to the intensive care unit for isolation and observation. Treatments were administered in accordance with local practice for COVID‐19. 3 Oral tacrolimus was also suspended, and low‐dose intravenous methylprednisolone was administered (40 mg, q12h).

Two days later, the patient's SpO2 was greater than 96%. On February 3, the reviewed examination still showed positive COVID‐19 RT‐PCR results. In response to this, oseltamivir phosphate capsules, cefoperazone, and sulbactam sodium were maintained. Five intermittent COVID‐19 RT‐PCR rechecks all showed positive results. However, the symptoms of fever, weakness, abdominal discomfort, and sleep disorders were all alleviated. On February 8, the patient's body temperature was basically normal. The antibody test for COVID‐19 showed levels of the IgM antibody were over 30 AU/mL, and the IgG antibody was 29 AU/mL. Both of these values were higher than baseline values. Moreover, pulmonary CT suggested the viral pneumonia was alleviated on February 14 (Figure 3B).

However, the bilirubin level became abnormal on February 17, with TBIL at 87.8 μmol/L, direct bilirubin 48.8 μmol/L, ALT elevated to 214 U/L, aspartate aminotransferase (AST) 122 U/L, and no fever developed. Since the tacrolimus had been suspended for 2 weeks, medical staff considered that the transplanted liver had begun to display the effects of rejection. For this reason, tacrolimus was administered (2 mg, q12h). Despite this, the serum TBIL level did not decline. It increased to 103.7 μmol/L, and ALT was 424 U/L on February 24. The patient was given large doses of intravenous methylprednisolone (300 mg for 3 days, progressively decreased to 20 mg). Finally, the acute rejection was under control, and the serum levels of TBIL, ALT, and AST declined gradually. However, after analysis of the patient's lymphocyte subtypes test, results showed that the patient was immunosuppressed the entire time, the absolute T lymphocyte count was between 313/μL and 495/μL, B lymphocyte count was between 41/μL and 99/μL, and the ratio of Th/Ts lymphocyte was between 0.52 and 0.80. Re‐examinations of the COVID‐19 RT‐PCR test after March 6 were all negative. On March 12, the patient was declared cured in accordance with clinical cure standards and discharged.

Case 2. A 48‐year‐old male patient was hospitalized on February 6, 2020, with the chief complaint of persistent fever for 10 days, with a peak temperature of 37.8°C, accompanied by cough, sputum, muscle aches, fatigue, and chest tightness. He was diagnosed with COVID‐19 2 days prior in the fever clinic; however, the treatment in clinic was not effective. The patient had received a living‐related donor renal transplantation in 2003 due to renal failure, and was taking oral immunosuppressants regularly after surgery (tacrolimus capsules 1 mg, qm +0.5 mg, qn, and Mycophenolate mofetil (MMF) 250 mg, qd).

Laboratory tests in clinic showed the following:

  • The count of peripheral WBC was 2.49 × 109/L, red blood cell was 2.98 × 1012/L, hemoglobin was 95 g/L, platelet was 86 × 109/L, lymphocyte was 0.64 × 109/L, and the level of serum creatinine was 138 μmol/L, and that of CRP was 31.25 mg/L. Peripheral leukocyte counts were below normal, especially lymphocyte count.

  • Pulmonary CT on admission showed bilateral scattered flocculent fuzzy lesions (Figure 3D).

  • Repeated COVID‐19–specific RT‐PCR on nasopharyngeal aspirate was again confirmed positive.

We treated him with oseltamivir, abidol, moxifloxacin, recombinant human interferon alpha (30 μg, qd), low‐dose methylprednisolone (40 mg, qd), and human immunoglobulin for intravenous injection (IVIG) (10 g, qd), together with symptomatic supportive treatment (Figure 2). The patient's symptoms were alleviated gradually, and so were the inspection results. Pulmonary CT re‐examination presented reduced flocculent fuzzy lesions; some were already fibrotic (Figure 3E).

However, results on March 2 showed that three series in peripheral blood decreased progressively:

  • The count of peripheral WBC was 2.05 × 109/L, lymphocyte was 0.5 × 109/L, red blood cell was 1.24 × 1012/L, hemoglobin was 41 g/L, platelet was 25 × 109/L, and the level of serum CRP grew to 101.79 mg/L.

  • The new COVID‐19 test continued to be positive.

  • However, the level of serum creatinine was lower (113.8 μmol/L).

MMF was suspended due to its potential bone marrow suppression, and only tacrolimus was still administered to maintain basal immunosuppression, at a concentration of around 2 ng/mL. Then we carried out a lymphocyte subset type test. After comprehensive treatments to control infection, a blood transfusion, and improvements in immunity, the pneumonia was alleviated, and the COVID‐19 RT‐PCR test was finally negative on March 20. Repeated tests after were still negative. Tacrolimus capsules were added to increase the concentration of FK506; it was kept around 4.5 ng/mL. However, there was no antibody produced until March 26. IgM and IgG all appeared positive. This patient successfully recovered from COVID‐19 and showed no signs of rejection during this long hospital stay. He was discharged on March 28.

 

Article - Respiratory infections in immunocompromised patients: Lung findings using chest computed tomography

 

Respiratory infections and subsequent complications are one of the leading causes of high mortality in immunocompromised patients.

Infections are very common in an immunocompromised host (ICH), which includes patients on chemotherapy (cancer), on immunosuppressive therapy (post transplantation patients, rheumatologic disorders) or acquired immunodeficiency diseases (AIDS, post-splenectomy), and their population is expanding globally.

Vaccines in Kidney Diseases

Article - Recommendations for the use of COVID-19 vaccines in patients with immune-mediated kidney diseases