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      COVID-19 in HIV: a Review of Published Case Reports

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          Abstract

          Patients with COVID-19 present with a myriad of comorbidities. An immunocompromised state like HIV in patients with COVID-19 can be life-threatening. We searched PubMed/Medline, Scopus, and Web of Science for case reports and case series about COVID-19 in HIV patients. We finally reviewed 20 case reports including cases of 43 patients with HIV and COVID-19. The mean age of 43 adult patients was 51.56 ± 27.56 years (range 24–76 years). Of these, 30 were male (69.77%), 11 were female (25.58%), and 2 were transgender (4.65%). A total of 25 patients (58.14%) were above 50 years of age. The most common cardiovascular comorbidities were hypertension and hyperlipidemia (48.8%), diabetes (20.93%), and morbid obesity (11.63%). Out of 43 HIV patients with COVID-19, 6 resulted in death (13.95%). All the patients who died were elderly above 50 years and required mechanical ventilation. HIV patients infected with COVID-19 had a high mortality rate. A high burden of pre-existing comorbidities and an advanced age in these patients make them prone to disease progression and worse outcomes.

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          COVID ‐19 and Older Adults: What We Know

          Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), a novel virus that causes COVID‐19 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin‐converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE‐2 receptor, the very receptor that the SARS‐CoV‐2 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID‐19 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID‐19 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926–929, 2020
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            COVID-19 in patients with HIV: clinical case series

            As of March 24, 2020, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has affected almost 400 000 people in 168 countries on five continents. Older patients (>60 years) and those with comorbidities (eg, hypertension, diabetes, cardiovascular disease, lung disease, and chronic kidney disease) present with more severe infection and worse prognosis. 1 Coronavirus disease 2019 (COVID-19) has been described in only one patient with HIV in Wuhan, China, 2 but case series in patients with HIV are lacking despite 37·9 million people having HIV globally. 3 Here we describe, to our knowledge, the first single-centre experience of COVID-19 in patients infected with HIV-1, including clinical characteristics, antiviral and antiretroviral treatment, and outcomes. All patients gave informed consent for publishing their clinical data. We used nasopharyngeal swab samples for all diagnoses, amplifying the betacoronavirus E gene and the specific SARS-CoV-2 RdRp gene by PCR. On March 9, 2020, 2 weeks into the COVID-19 outbreak in Spain, 543 consecutive patients with SARS-CoV-2 infection had been admitted to hospital at Hospital Clínic Barcelona, Barcelona, Spain. We admitted 62 (12%) into intensive care units and we discharged 208 (38%) with supervised outpatient care. Of all patients, five (0·92%; 95% 0·39–2·14) were HIV positive (table ), of whom three were male and two were transgender, and four identified as men who have sex with men (MSM). Two patients had comorbid conditions. Two patients were sex workers. Four were virologically suppressed: two with protease-inhibitor (darunavir-boosted cobicistat) and two with integrase-inhibitor (dolutegravir)-based antiretroviral therapy (ART). CD4 counts were above 400 cells per μL in all patients apart from patient 5, who was ART naive and a very advanced late presenter. Two patients had upper-respiratory tract infections, and three had viral pneumonia, including two requiring admission to the intensive care unit with invasive (patient 2) and non-invasive (patient 5) mechanical ventilation. Table Demographics, clinical characteristics at admission, treatment, and outcomes of five patients with HIV and COVID-19 Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Demographics and baseline HIV status Age (years) 40 49 29 40 31 Gender Transgender Male Male Male Transgender HIV-risk factor and exposure MSM, gym worker Bisexual man, health-care worker MSM, sexual worker participant in ChemSex session 6 days before MSM, dinner 5 days before with another person who was COVID-19 positive MSM, sexual worker Comorbidities* None Hypothyroidism None Asthma None HIV status Year of HIV diagnosis 2007 2003 2013 2003 2020 Last CD4 cell count (cells per μL) 616 445 604 1140 13 Last CD4:CD8 ratio 0·8 0·46 1·1 1·2 0·1 HIV viral load at or before admission (copies per mL) 10 000 400 300 ND Ferritin (ng/mL) ND 1020 ND 1044 866 Procalcitonin (ng/mL) ND ND <0·03 ND ND Severity of the infection at admission Mild Severe Mild Moderate Severe Treatment and outcomes ART† ART at admission maintained Tenofovir disoproxil fumarate, and emtricitabine plus lopinavir-boosted ritonavir (on going) Tenofovir disoproxil fumarate, and emtricitabine plus lopinavir-boosted ritonavir (for 3 days) Tenofovir disoproxil fumarate, and emtricitabine plus lopinavir-boosted ritonavir (for 14 days) Tenofovir alafenamide, emtricitabine, and darunavir-boosted cobicistat (on going) Other antiviral treatments No Interferon beta-1b (for 7 days), hydroxychloroquine (for 7 days) Hydroxychloroquine (for 5 days) Hydroxychloroquine (for 5 days) Interferon beta-1b (for 4 days), hydroxychloroquine (for 5 days) Other antibiotics No Meropenem (for 16 days), linezolid (for 14 days) Azithromycin (for 5 days) Azithromycin (for 5 days), cefixime (for 5 days) Azithromycin (for 5 days), ceftaroline fosamil (for 7 days), co-trimoxazole (for 21 days, followed by secondary prophylaxis) Admitted to an intensive care unit No Yes No No Yes Invasive or non-invasive mechanical ventilation No Invasive No No Non-invasive Corticosteroids or tocilizumab No Tocilizumab, 400 mg one single dose (on day 10) No Inhaled corticosteroids Corticosteroids Length of hospital stay (days) 1 21 3 4 12 Length of home hospitalisation (days)‡ 13 .. .. 10 .. Outcomes Cured Still at hospital Cured Cured Cured Additional comments .. Extracorporeal membrane oxygenation since day 13 (on going) .. .. Concomitant Pneumocystis jiroveci and bacterial pneumonia treatment Lopinavir-boosted ritonavir was given as 400 mg of ritonavir boosted with 100 mg of lopinavir twice a day for 14 days; azithromycin was given as 500 mg once a day, with a loading dose on the first day, and then 250 mg once a day for 4 days; hydroxychloroquine was given as 400 mg twice a day with a loading dose on the first day and then 200 mg twice a day for 4 days, and interferon beta-1b was given as 250 μg (8 million units) every 48 h. MSM=men who have sex with men. ND=Not done. * Hepatitis C virus, hepatitis B virus, chronic obstructive pulmonary disease, asthma, chronic kidney failure, hypertension, cardiovascular disease, diabetes, solid organ transplantation, use of biologics, other types of immunosuppression. † Tenofovir alafenamide, emtricitabine, and darunavir-boosted cobicistat was indicated before the information provided by Janssen on March 18, 2020. ‡ Discharged with a supervised home-care programme. We started all five patients on anti-SARS-CoV-2 treatment on the day of diagnosis. We gave all five patients boosted-protease inhibitor ART. We explained to patients treated with ART that we were making a transitional change in their regimen on the basis of the fact that HIV protease inhibitors might have activity against the coronavirus protease and that once the treatment ended they would return to their usual regimen. Patient 1 with darunavir-boosted cobicistat, and patients 2–4 were adapted to lopinavir-boosted ritonavir. We gave patient 5 darunavir-boosted cobicistat. We left patient 1, who had mild infection, on his normal ART. We gave the other patients hydroxychloroquine (patients 2, 3, 4, and 5) with azithromycin (patients 3, 4, and 5), and interferon beta-1b (patient 2 and 5). No patients were given remdesivir (only available through clinical trials, with restricted access at the time these patients were evaluated). We administered concomitant antibacterials in all three patients who had pneumonia (patients 2, 4, and 5), and corticosteroids in two patients (patients 4 and 5) and tocilizumab in one (patient 2). We have discharged four patients (80%); one remains in hospital in the intensive care unit (patient 2). Our preliminary experience highlights several issues. First, patients with HIV accounted for almost 1% of patients with COVID-19 who required admission to hospital in Barcelona. We only observed the infection in people younger than 50 years, who identified as MSM, and who have a COVID-19 clinical pictures resembling the general population. None of these five patients has died, although we admitted two to intensive care, where one remains. More studies of COVID-19 in patients with HIV are needed in the older MSM population, drug users, and heterosexual men and women in middle-income and lower-income settings. Second, two patients who were MSM were sex workers, one reporting participating in a chemsex party 6 days before admission to hospital. During this pandemic, implementing health education programmes is very important to explain that such activities as these could cause clusters of SARS-CoV-2 transmission. Third, we adapted ART in all patients to a regimen based on protease inhibitors: three patients were given lopinavir-boosted ritonavir and two were given darunavir-boosted cobicistat. In the past month, a clinical trial 4 found that lopinavir-boosted ritonavir was ineffective as a monotherapy against severe pneumonia associated with COVID-19 in China. Therefore, investigation of the efficacy of this treatment in patients with COVID-19 in combined therapy in earlier stages of the disease is needed. Additionally, Janssen reported on March 18, 2020, that darunavir was ineffective against SARS-CoV-2 due to low affinity to coronavirus protease. Fourth, we did not give our patients remdesivir, the most active in-vitro and in-vivo antiviral drug against coronavirus to date, 5 and is currently only available through clinical trials or for compassionate use. This drug has no pharmacokinetic interactions with any medication including ART drugs. Finally, in advanced patients (ie, late presenters), we must ensure differential diagnosis and initial antimicrobial treatment to address pulmonary opportunistic infections (eg, Pneumocystis jirovecii, as seen in patient 5) presenting with similar clinical and radiological symptoms. This pandemic is a challenge affecting everyone. By generating information such as we present here, the management and prognosis of patients co-infected with HIV and SARS-CoV-2 might be improved.
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              Use of Convalescent Plasma Therapy in Two COVID-19 Patients with Acute Respiratory Distress Syndrome in Korea

              Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus-2 not yet has established its treatment, but convalescent plasma has been expected to increase survival rates as in the case with other emerging viral infections. We describe two cases of COVID-19 treated with convalescent plasma infusion. Both patients presented severe pneumonia with acute respiratory distress syndrome and showed a favorable outcome after the use of convalescent plasma in addition to systemic corticosteroid. To our knowledge, this is the first report of the use of convalescent plasma therapy for COVID-19 in Korea.
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                Author and article information

                Contributors
                sandeepkcsingh@gmail.com
                Journal
                SN Compr Clin Med
                SN Compr Clin Med
                Sn Comprehensive Clinical Medicine
                Springer International Publishing (Cham )
                2523-8973
                2 November 2020
                2 November 2020
                : 1-11
                Affiliations
                [1 ]Washington University of Health and Science, San Pedro, Belize
                [2 ]Carefirst Primary and Wellness Center, Dallas, TX USA
                [3 ]UT South Western Medical Center, Dallas, TX USA
                [4 ]GRID grid.415249.f, ISNI 0000 0004 0648 9337, Princess of Wales Hospital, ; Bridgend, UK
                [5 ]Vydehi Institute of Medical Sciences and Research Center, Bangalore, India
                [6 ]GRID grid.5650.6, ISNI 0000000404654431, Department of Clinical Epidemiology, Biostatistics and Bioinformatics, , Amsterdam University Medical Center, AMC, ; Amsterdam, Netherlands
                [7 ]GRID grid.415285.f, Department of Medicine, , Gandhi Medical College, ; Secunderabad, Telangana India
                [8 ]GRID grid.414026.5, ISNI 0000 0004 0419 4084, Division of Cardiology, , Atlanta VA Medical Center, ; Decatur, GA USA
                Author information
                http://orcid.org/0000-0001-9338-1209
                Article
                593
                10.1007/s42399-020-00593-6
                7604227
                33163861
                4dbb80f9-24a9-4c51-bab0-4154ee468e48
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 13 October 2020
                Funding
                Funded by: Amsterdam UMC (University of Amsterdam)
                Categories
                Covid-19

                covid-19,hiv,sars-cov-2
                covid-19, hiv, sars-cov-2

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