On World AIDS Day, advocates in the Battlefords gathered to raise awareness about how the virus affects people in their community — and how people can get help and treatment, if they need it.
Skin microbiome research could lead to new approaches for addressing organ damage after stem cell transplants.
Organ damage occurs in up to 70% of patients in the first few months following stem cell transplant.
The reasons for this potentially life-threatening reaction have long been the subject of scientific research.
Now, researchers led by Georg Stary from the Department of Dermatology at MedUni Vienna and Vienna General Hospital in collaboration with the Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases have identified bacterial proliferation on the skin as a factor associated with the occurrence of the complication.
The findings recently published in the medical journal Leukemia contribute to the research and development of new therapeutic approaches.
The researchers came to their findings by examining the skin of 50 patients, most of whom had undergone stem cell transplant (SCT) for leukemia at the Department of Bone Marrow Transplantation at the Department of Internal Medicine I at MedUni Vienna and Vienna General Hospital.
In the first few weeks or months after receiving the stem cells from the donor, a donor-versus-recipient reaction (graft-versus-host disease, GVHD) occurred in some of the test subjects. When the microorganisms on the skin (skin microbiome) of those affected were analyzed in detail, the research team led by first author Nadine Bayer and study leader Georg Stary from MedUni Vienna and Vienna General Hospital found a drastic decrease in bacterial abundance.
“The reduction in proliferation was particularly pronounced in severe cases of GVHD – even before symptoms appeared,” Georg Stary reported on key findings. At the same time, the scientists observed an increased occurrence in patients with GVHD of staphylococci on the skin, and these are bacteria that can cause serious infections.
Despite precise examinations of the stem cell donors’ and recipients’ tissue characteristics as well as preventive medication, GVHD occurs in approximately 30% of patients after sibling donations and in approximately 70% of patients after donations from unrelated donors. This reaction means that body cells are attacked as foreign by immune cells that are newly developed from the transplant, and organs are subsequently damaged. The complication almost always affects the skin: the first symptoms are usually rashes, which, depending on the severity, can manifest themselves as slight redness or severely inflamed cutaneous changes with a detachment of the uppermost skin layer.
The fact that the composition of the gut microbiome influenced the clinical course after stem cell transplantation was already known to medical researchers. With the identification of the skin microbiome in GVHD, the scientists have another tool at their disposal with which to research and develop improved treatment measures.
“Follow-up studies will now show whether the change in the skin microbiome may contribute to the development of GVHD and whether new therapeutic approaches can be identified from the knowledge gained,” said study leader Stary.
An unprecedented public health emergency is unfolding worldwide with the coronavirus disease 2019 (COVID-19) pandemic.1 After COVID-19 emerged, concern was voiced regarding its impact on people living with HIV.2 Some of the factors that increase susceptibility to human immunodeficiency virus (HIV) are also relevant for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes COVID-19.3,4 Certain comorbidities were stronger drivers of COVID-19 outcomes and were associated with an increased risk of death.5
Opportunistic infections (OIs) are a leading cause of mortality in patients with acquired immunodeficiency syndrome (AIDS). Worldwide, tuberculosis (TB) is the predominant cause of death from an infectious disease, causing more deaths than HIV/AIDS. However, the HIV pandemic has worsened the situation not only by leading to the resurgence of TB but also by suppressing the host immune system, which provides an opportunity for infection by non-TB mycobacteria (NTM).6
The most common NTM species that causes disseminated infections in patients with HIV/AIDS is Mycobacterium avium complex (MAC). HIV patients with disseminated MAC infection are at high risk of developing complications and have a higher mortality risk, thus necessitating more active clinical management.7 M. avium is one of the main causes of NTM infection-associated morbidity and mortality in HIV/AIDS patients.8 MAC infections have clinical symptoms similar to active TB infections and are therefore easily mistaken for TB.
Candidiasis are commensal fungi of the oral mucosa often found in immunocompromised patients and are potential pathogens that can cause an OI. In HIV-1 and TB co-infected patients, oral candidiasis (OC) is found with a prevalence of 35%, and in HIV-1 patients with OC, there is a 2.4 times higher odds of having TB.9
In this report, we retrospectively describe a 23-year-old woman who was diagnosed with HIV 17 years prior. This patient had concurrent SARS-CoV-2, MAC, and OC infections. We present the diagnosis and management of these infections that allowed the patient’s recovery.
The patient was a 23-year-old woman who had been diagnosed with HIV 17 years prior and had since received standard antiretroviral therapy (ART). Notably, she had switched from first line to simplified dual regimen (abacavir-lamivudine-efavirenz to lamivudine-dolutegravir) due to adverse events. She was diagnosed with TB five months prior, when her sputum smear was positive for acid-fast bacilli and the sputum culture subsequently grew TB. She was treated with rifampin, isoniazid, ethambutol, and pyrazinamide. According to “Chinese Guidelines for HIV/AIDS Diagnosis and Treatment”,10 when she was diagnosed with SARS-CoV-2 infection, she was in the AIDS stage due to poor adherence to antiretroviral medications with an HIV load of <100 viral copies/mL and a CD4+ T-cell count of 7 cells/µL.
On hospital day 1, the patient had a positive PCR test for SARS-CoV-2 in a hospital screening. She was referred to a local hospital with constitutional symptoms, including intermittent fever with chills. She had no cough or expectoration but was diagnosed with anemia and TB 5 months prior. There were no retrievable previous trends to compare.
On hospital day 6, the patient was transferred to the Southern Hospital of Zhengzhou First People’s Hospital. She had fever and chills, her temperature was 39.0°C at admission, and her SPO2 was 100% (without oxygen inhalation). She had density shadows in both lungs but had no respiratory distress and had normal oxygen saturation. The patient was found to have normochromic anemia with a hemoglobin level of 85 g/L. Additional blood test results are presented in Table 1. TB and COVID-19 were managed with azithromycin, moxifloxacin, isoniazid, rifabutin, and ethambutol, and ART was continued with lamivudine and dolutegravir. Anemia was treated by transfusion with suspended red blood cells. On hospital day 8, chest computed tomography (CT) scanning revealed substantial pulmonary lesions (Figure 1).
Table 1 Clinical Laboratory Results at Admission and Throughout the Clinical Course of Infection
Figure 1 CT scanning revealed substantial pulmonary lesions.
On hospital day 13, the patient reported fever (temperature of up to 38.8°C), but no cough, sputum cough, chest tightness, or shortness of breath. Laboratory tests results are presented in Table 1. A diagnosis of disseminated MAC infection was made by two sputum cultures positive for MAC. Co-infection is a high-risk factor for the progression of COVID-19 to severe and the patient was treated with BRII-196+BRII198 monoclonal antibody therapy. MAC was managed with moxifloxacin, azithromycin, rifabutin and ethambutol, sulfamethoxazole given orally this compound also helps to prevent pneumocystis pneumonia (PCP). Thymalfasin was given to improve immunity, low molecular weight heparin calcium was given as an anticoagulant therapy, and the other treatments described above were continued. On hospital day 16, the chest CT scan showed a thin ground-glass density shadow in both lungs, but it was slightly smaller than in previous scans (Figure 2). Laboratory tests showed C-reactive protein (CRP) of 87.6 mg/L. Azithromycin and moxifloxacin were added to the treatment protocol for anti-infection treatment, and amikacin was used as an anti-MAC treatment.
Figure 2 CT scan showed a thin ground-glass density shadow in both lungs, but it was slightly smaller than in previous scans.
On hospital day 27, the patient had intermittent fever and pain in the left abdomen and the blood test results are presented in Table 1. Chest CT scanning was performed, which showed significant improvement of the pulmonary lesions (Figure 3). On hospital day 31, the patient received convalescent plasma therapy.
Figure 3 CT scanning showed significant improvement of the pulmonary lesions.
During days 35–48 of hospitalization, the patient had stable signs and did not have cough, fever, chest tightness, or shortness of breath. The treatments described above were continued.
During days 49–54 of hospitalization, the patient had scattered leukoplakia on the oral mucosa and received fluconazole injection as an antifungal treatment and a sodium bicarbonate gargle. She received a nebulized inhalation of 2 mL of sterilized water and was administered a twice-daily injection of recombinant human interferon α. On hospital day 54, a throat swab was submitted for fungal culture and returned a positive result for Candida albicans infection. The above treatments were continued.
On days 65–67 of hospitalization, two sequential PCR tests for SARS-CoV-2 returned negative results. Three consecutive days of examination showed negative results. The patient was discharged in accordance with the “Diagnosis and Treatment Plan for New Coronavirus Infected Pneumonia (Trial Seventh Edition)”.11
A thorough history-taking and examination, as well as the appropriate use of clinical tools, are crucial for identifying concomitant OIs in immunosuppressed patients.
A longer course of COVID-19 has been reported in the setting of co-infection with HIV, particularly with low CD4 cell counts, low CD4+ levels and high levels of viral load influence the lethal progression of COVID-19.7,8,12 SARS-CoV-2 might damage lymphocytes, especially T lymphocytes, and the immune system was impaired during the period of disease.13 HIV-1 infection skewed the SARS-CoV-2 T cell response, HIV-1 mediated CD4+ T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2, and a decrease in the polyfunctional capacity of SARS CoV-2 specific CD4+ T cells was observed in COVID-19 patients.14 Our patient had multiple individual risk factors associated with prolonged viral shedding as well as a risk of severe SARS-CoV-2: advanced HIV with a low CD4 count. This maybe the reasons that over two months of intense treatment her CD4+ T cell and total lymphocyte counts remained very low, and her immune system did not improve.
The probability of an OI increases as the CD4+ T cell count declines, especially at counts below 200 cells/µL.15 This patient had switched from first line to simplified dual regimen (abacavir-lamivudine-efavirenz to lamivudine-dolutegravir) due to adverse event. She was in the AIDS stage due to poor adherence to antiretroviral medications and virological failure, with an HIV load of <100 viral copies/mL and a CD4+ T cell count maintained at <100 cells/µL, which may have contributed to the incidence of OIs. MAC are seen more commonly in patients with CD4+ T cell counts of <50 cells/µL.16 The risk of developing MAC infection increases in the presence of other concurrent infections such as TB.17 In AIDS patients, MAC infections often present clinically as disseminated MAC, with several weeks of early symptoms, such as prolonged fever, fatigue, weight loss, abdominal pain, diarrhea, and hepatosplenomegaly. MAC diagnoses are often delayed due to the nonspecific presentation of MAC pulmonary disease and radiological findings that overlap with other pulmonary diseases.18 Patients with risk factors and who meet the diagnostic criteria – which include clinical, radiological, and microbiological criteria – should be considered for treatment. In this case, disseminated MAC infection was diagnosed after two sputum MAC positive cultures over a period of two weeks, indicating that attention should be paid to the diagnosis. Oral candidiasis as a potential harbinger of T and B cell immunosuppression associated with viral infections and COVID-19 may be a risk factor for candidiasis.19 The practitioner should be aware of the importance of unexplained oral candidiasis associated with viral infections. PCP is a life-threatening opportunistic infection that can occur in immunodeficient individuals. The PCP mortality rate can reach 60% if the diagnosis is delayed.20 Early prevention reduces the incidence of PCP. In our case, PCP infection was prevented. This patient’s CD4+ T-cell count was below 200 cells/µL, and sulfamethoxazole was given orally to prevent PCP infection.
In terms of treatment, the use of monoclonal antibody therapy, ART, and broad-spectrum antibiotics is in line with recent literature for the treatment of COVID-19 in patients with impaired immune system functions. Neutralising monoclonal antibody therapies targeting SARS-CoV-2 accelerate reduction in viral loads and reduce the risk of disease progression for outpatient with mild COVID-19.14 Co-infection is a high-risk factor for the progression of COVID-19 to severe and the patient was treated with BRII196+BRII198 monoclonal antibody therapy. The only medication that has not been administered is steroids, which has an important reducing factor in lung injuries and was demonstrated to have better results regarding mortality rate in patients with moderate and severe COVID-19.21,22 However, at the time of the patient’s acquisition of severe immunosuppression and COVID-19, the main studies on the impact of steroids on COVID-19 mortality had not been published. Therefore, the patient did not receive steroids during hospitalization. Considering that our patient was diagnosed SARS-CoV-2 infection in a hospital screening, we speculated that in our patient, COVID-19 had existed for a long time before presentation.
There is a paucity of data on SARS-CoV-2 infection in people with HIV and low CD4 counts. Most studies have been retrospective cohort analyses of patients who are more likely to be virally suppressed and less likely to have CD4 counts of more than 200 cells per μL.9,23 In our cases illustrate that OIs is an important consideration in the presence of one in the setting of co-infection of advanced HIV disease and COVID-19. When treating immunocompromised individuals, some opportunistic infections, such as PCP, should be prevented in the presence of risk factors, these treatments may help reduce clinical symptoms and improve prognosis.
Written informed consent was obtained from the patient for publication of this case report and any accompanying images. The institutional approval was not required for the publication of the case details.
This work was supported by Henan Province COVID-19 Traditional Chinese Medicine Scientific Research Special Project (2022ZYFY02), the Nation Natural Science Foundation of China(U1904153), Science and Technology Research Project of Henan Province (222102310570) and Henan Province Special Project of Traditional Chinese Medicine Scientific research(2019AZB006,2019JDZX2096).
The authors declare that there are no competing interests in this work.
1. Fauci AS, Lane HC, Redfield RR. Covid-19 – navigating the uncharted. N Engl J Med. 2020;382(13):1268–1269. doi:10.1056/NEJMe2002387
2. Ballester-Arnal R, Gil-Llario MD. [The Virus that Changed Spain: impact of COVID-19 on People with HIV]. El Virus que cambió España: impacto del COVID-19 en las personas con VIH. AIDS Behav. 2020;24(8):2253–2257. Spanish. doi:10.1007/s10461-020-02877-3
3. Belaunzaran-Zamudio PF, Caro-Vega Y, Giganti MJ, et al. Frequency of non-communicable diseases in people 50 years of age and older receiving HIV care in Latin America. PLoS One. 2020;15(6):e0233965. doi:10.1371/journal.pone.0233965
4. Deeks SG. Immune dysfunction, inflammation, and accelerated aging in patients on antiretroviral therapy. Top HIV Med. 2009;17(4):118–123.
5. Johnston R. The first 6 months of HIV-SARS-CoV-2 coinfection: outcomes for 6947 individuals. Curr Opin HIV AIDS. 2021;16(1):54–62. doi:10.1097/coh.0000000000000654
6. Kali A, Charles MP, Noyal MJ, Sivaraman U, Kumar S, Easow JM. Prevalence of Candida co-infection in patients with pulmonary tuberculosis. Australas Med J. 2013;6(8):387–391. doi:10.4066/amj.2013.1709
7. Wang M, Luo L, Bu H, Xia H. One case of coronavirus disease 2019 (COVID-19) in a patient co-infected by HIV with a low CD4(+) T-cell count. Int J Infect Dis. 2020;96:148–150. doi:10.1016/j.ijid.2020.04.060
8. Huang J, Xie N, Hu X, et al. Epidemiological, virological and serological features of coronavirus disease 2019 (COVID-19) cases in people living with human immunodeficiency Virus in Wuhan: a Population-based cohort study. Clin Infect Dis. 2021;73(7):e2086–e2094. doi:10.1093/cid/ciaa1186
9. Vizcarra P, Pérez-Elías MJ, Quereda C, et al. Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort. Lancet HIV. 2020;7(8):e554–e564. doi:10.1016/s2352-3018(20)30164-8
10. Hepatitis C Research Group CSoIDCCfDCaP. Chinese guidelines for HIV/AIDS diagnosis and treatment. Chin J AIDS STD. 2021;27(11):1182–1201. doi:10.13419/j.cnki.aids.2021.11.02
11. China GOoNHCotPsRo. Diagnosis and treatment protocol for novel coronavirus pneumonia (trial version 7). China Med. 2020;15(06):801–805.
12. Ambrosioni J, Blanco JL, Reyes-Urueña JM, et al. Overview of SARS-CoV-2 infection in adults living with HIV. Lancet HIV. 2021;8(5):e294–e305. doi:10.1016/s2352-3018(21)00070-9
13. Qin C, Zhou L, Hu Z, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71(15):762–768. doi:10.1093/cid/ciaa248
14. Riou C, Stek C, Daroowala R, et al.; HIATUS consortium. Efficacy and safety of two neutralising monoclonal antibody therapies, sotrovimab and BRII-196 plus BRII-198, for adults hospitalised with COVID-19 (TICO): a randomised controlled trial. Lancet Infect Dis. 2022;22(5):622–635. doi:10.1016/s1473-3099(21)00751-9
15. Buchacz K, Lau B, Jing Y, et al. Incidence of AIDS-defining opportunistic infections in a multicohort analysis of HIV-infected persons in the United States and Canada, 2000–2010. J Infect Dis. 2016;214(6):862–872. doi:10.1093/infdis/jiw085
16. Palella FJ Jr, Delaney KM, Moorman AC, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med. 1998;338(13):853–860. doi:10.1056/nejm199803263381301
17. Kaplan JE, Benson C, Holmes KK, Brooks JT, Pau A, Masur H. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. MMWR Recomm Rep. 2009;58(Rr–4):1–207.
18. Daley CL, Winthrop KL. Mycobacterium avium complex: addressing gaps in diagnosis and management. J Infect Dis. 2020;222(Suppl 4):S199–S211. doi:10.1093/infdis/jiaa354
19. Katz J. Prevalence of candidiasis and oral candidiasis in COVID-19 patients: a cross-sectional pilot study from the patients’ registry in a large health center. Quintessence Int. 2021;52(8):714–718. doi:10.3290/j.qi.b1491959
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On World AIDS Day, advocates in the Battlefords gathered to raise awareness about how the virus affects people in their community — and how people can get help and treatment, if they need it.
“HIV is completely preventable in today’s society, with all the advances in medication,” said Battle River Treaty 6 Health Centre’s HIV project coordinator, Cymric Leask. “But due to a lot of intersecting factors — especially due to COVID — in the past couple of years, our HIV numbers have skyrocketed.”
In 2021, more than 200 new cases of HIV were diagnosed in the province — even while testing, treatment and outreach were reduced during the height of the COVID-19 pandemic.
Saskatchewan has the highest rate of new HIV infections in Canada, and has had the highest annual rate in the country for more than a decade.
The proportion of new HIV cases in rural areas is rising, too.
“Here up north, there are such large barriers to access to care,” said Leask. “We do have some great resources here in North Battleford … but it’s still very hard to access the proper care for HIV.”
For example, getting started on HIV medication requires a visit with a communicable disease doctor — but there is no communicable disease doctor based in the Battlefords. Instead, that doctor visits the community only once every four months.
Another barrier Leask has found is that many people still have an outdated understanding of what HIV is, who is at risk and how treatment works.
“Especially here in rural areas, it’s stigmatized as something that only affects gay or bisexual men — men who have sex with men,” Leask said.
Today in Saskatchewan, men and women are diagnosed with HIV at almost equal rates, and two thirds of new cases are passed through injection drug use.
Treatments are much easier to manage than they used to be; some only involve taking one pill a day.
But the enduring stigma around HIV makes it harder for people to find community and support.
“People don’t talk about it,” said Jackie Kennedy, executive director of the Battlefords Indian and Métis Friendship Centre. “I think they’re afraid to. A lot of people don’t disclose that information (about their HIV status) because they are afraid to be judged.”
As more people continue to be diagnosed with HIV in Saskatchewan every year, groups and organizations in the Battlefords are working hard to make it easier for people to get testing, treatment, information and harm reduction supplies.
“We want to banish that stigma of how it used to be,” said Leask. “It’s not like that anymore.”
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Haldimand-Norfolk’s acting medical officer of health is urging residents to get their flu shot as soon as possible.
“The hospital system in Ontario is currently overwhelmed with individuals seeking care for influenza and other respiratory viruses,” Dr. Matthew Strauss said Thursday. “There is strong evidence that influenza vaccination can prevent trips to the ER (emergency room) for flu.
“I strongly recommend that you get your flu shot ASAP on this basis, particularly if you are in a high risk group.”
Flu shots are available through local pharmacies and health care providers. Children six months to two years can only get their flu shot from a doctor or nurse practitioner.
Those in the high-risk group for complications and hospitalization because of the flu include: babies and children under five; people 65 and older; people who are pregnant; people with underlying health conditions and residents of nursing homes and other chronic care facilities.
The Haldimand-Norfolk Health Unit on Thursday said it has received a significant number of positive lab results related to influenza in recent weeks.
The health unit has received notification of 141 lab-confirmed flu cases in Haldimand or Norfolk residents between Oct. 11 and Nov. 29. During the same period of the 2019-2020 flu season there was just one confirmed case in Haldimand or Norfolk.
The flu is a virus that affects the nose, throat and sometimes the lungs. Although some who get the flu will not have any symptoms or suffer mild illness, others, especially the elderly or young children, can become seriously ill from the flu.
The virus spreads by droplets from coughs or sneezes from someone who is sick with the flu. As well, it can spread if someone touches surfaces where these droplet have landed and then they touch their mouth, nose or eyes.
Steps to protect yourself from the flu include getting vaccinated each year. Other measures including staying home and way from others if you feel sick, improving ventilation in indoor and shared spaces and frequent hand-washing with soap, water or hand sanitizer.
Washing your hands before touching your eyes, nose or mouth is also beneficial.
The health unit also recommends cleaning and disinfecting frequently touches surfaces and objects.
Clean and disinfect frequently touched surfaces and objects.
Meanwhile, anyone with symptoms of a respiratory illness should stay home until the fever subsides and symptoms have been improving for at least 24 hours and 48 hours if you have had nausea, vomiting or diarrhea.
Those with symptoms should not be visiting people in hospitals, retirement, long-term care homes or any facilities that includes people at higher risk of illness. Those experiencing severe or worsening symptom or in a high-risk group should seek medical attention.
For more information about the influenza virus and the flu shot, visit www.hnhu.org/ .
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