COVID-19 and HIV co-infection
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Harmeet Kharoud M.D.[2]
Synonyms and keywords:
Overview
- An observational prospective study found out that the incidence of HIV-infected individuals to be affected by SARS-CoV-2 was similar to the general population.
- Specific antiretroviral therapy did not affect COVID-19 severity.
- Immunosuppression(low CD4 cell counts) was associated with COVID-19 severity.
- Patients with HIV infection often have other comorbidities(lung disease, cardiovascular disease) therefore, increasing the risk for severe-COVID-19 disease.
- Patients with HIV infection with CD4 cell count<200/mm3 are at increased risk for complications from other respiratory infections. However, we do not know if this is the scenario with COVID-19
Historical Perspective
- COVID-19 caused by SARS-CoV-2 was first identified in late December 2019 in Wuhan, Hubei China.
- Due to its rapid spread worldwide from person to person it was declared as a pandemic by WHO on March 11, 2020. another most dangerous virus causing acquired immunodeficiency syndrome (AIDS). According to WHO, there are ~37.9 million people living with HIV.[1]
- On March10, 2020 CDC mentioned that people with HIV would be at increased risk for severe COVID-19 infection.[2]
- On March 11, 2020, the first case study was published on a person living with HIV who developed and recovered from COVID-19.[3]
- On March 20, US Department of Health and Human services posted interim COVID-19 guidance for HI positive individuals.[4]
- On April 15, the first case series was published in people living with HIV who developed COVID-19.[5]
- On May 28 a prospective study was published in Lancet describing the epidemiology and clinical characteristics of the COVID-19 in HIV individuals.[6]
Pathophysiology
- COVID-19 is caused by the SARS-CoV-2 virus which enters into the cells by attacking its primary receptor, Angiotensin-converting enzyme 2. ACE-2 receptors are expressed in pulmonary tissues and extrapulmonary system tissues(heart, kidney, endothelium, and intestine).[7]
- Patients with HIV with co-existing underlying comorbidities like diabetes mellitus, hypertension, etc may have increased expression of ACE-2 receptors in the tissues causing increased binding of SARS-CoV-2 virus and replication leading to high viral load.
- Exact mechanism of interaction of SARS-CoV-2 virus and HIV virus is unclear but it is suspected that since both of the virus cause immune deficiency, they might be causing more severe immuological consequence.
- It is also suspected that defective cellular immunity in people living with HIV might be protective for severe cytokine dysregulation, observed in patients with COVID-19
- High viral load of SARS-CoV-2 virus could lead to manifestations of pneumonia, cardiac dysfunction, multi-organ dysfunction
Causes
COVID-19 infection in HIV infected individuals is caused by SARS-CoV-2 virus
Differentiating from other disease
COVID-19 infection in HIV individuals should be differentiated from other opportunistic infections and other respiratory infections such as Influenza, Parainfluenza, and other common respiratory illnesses
Epidemiology and Demographics
- Different studies have not shown any difference in the incidence rate of COVID-19 in HIV individuals as compared to the general population.
- A prospective observational study of 2873 HIV individuals showed an incidence of the rate of COVID-19 in HIV individuals of 17.7 cases per 1000 population.[4]
Age
Gender
- Study found that the majority of people living with HIV who developed COVID-19 were male.[4]
Race
There is insufficient information regarding race-specific prevalence or incidence HIV SARS-CoV-2 coinfection.
Comorbitdities
There is increased prevalence of comorbidities in HIV–SARS-CoV-2 co-infected individuals. They are associated with following comorbidities.[6]
- Hypertension
- Cardiovascular disease
- Diabetes
- Chronic kidney disease
- Chronic liver disease
- Chronic respiratory disease.
- High BMI
Risk Factors
At present people with HIV who are at greatest risk of Severe COVID-19 infection are people[4] -
- who have low CD4 cell count.
- not on antiretroviral therapy.
Specific Populations with HIV at risk for COVID-19
Pregnancy
- Pregnant individuals with HIV are at greater risk for severe illness, morbidity, or mortality as compared with the general population due to coronavirus infections(SARS-CoV and MERS-CoV) and other viral respiratory infections like influenza. [8]Data related to COVID-19 is limited but pregnant individuals with HIV are suspected to be at greater risk due to SARS-COV-2 similarity with other coronaviruses (SARS-CoV and MERS).[9][10]
- They are suspected to be at increased risk of preterm delivery, adverse neonatal outcomes.[9] In a small series of pregnant women with COVID-19 adverse outcomes such as fetal distress and preterm delivery have been noted. They have also been reported with SARS-CoV and MERS.[11][12][13]
- Vertical Transmission of COVID-19 has not been found.[14][15][16][17]
Older Adults
- Older adults(>50 years age) with HIV have a greater risk of having co-existing comorbidity including diabetes, hypertension, cardiovascular disease, and chronic lung disease as compared with general population. Therefore, older adults with HIV are suspected to be at an increased risk of COVID-19 infection.[18]
- It is recommended that they follow the recommendations outlined for patients with HIV.
Screening
There is insufficient information regarding screening of COVID-19 in people living with HIV.
Natural History, Complications and Prognosis
Natural History
- If left untreated it might lead to pneumonia and multi-organ failure.
Complication
- HIV SARS-CoV-2 coinfection could lead to large number of complications similar to general population.
Diagnosis
Diagnostic Criteria
- The diagnosis of COVID-19 in HIV patients remains the same as compared to the general population.[8][10]
- The challenge of diagnosing COVID-19 in HIV patients is to clinically distinguish it from common mimickers such as Influenza, Parainfluenza, and other common respiratory illnesses. Currently, history of exposure and epidemiological risk factors are the two biggest historical cues, aside from respiratory symptoms, that can guide clinician into considering COVID-19 in the differential diagnosis.
Diagnostic Study of Choice
- RT-PCR is the standard diagnostic of choice to confirm cases and for active COVID-19 cases. It may take up to 8 weeks for RT-PCR to become negative, and so a repeat RT-PCR is no longer required to document recovery.[19]
- Antibody tests are helpful in detecting previous COVID-19 infection and are likely to be most useful if used within 15 days or more after the onset of symptoms[20]
History and Symptoms
- There hasn't been any observable difference in clinical presentation among people with HIV infection as compared to the general population.
- Common symptoms for COVID-19 are[4]
Laboratory Findings
HIV individuals with coinfection with COVID-19 are associated with following laboratory findings[4]
- High ESR
- Lymphopenia
- Neutrophilia
- Anemia
- Thrombocytopenia
- Abnormal fibrinogen
- Hypoalbuminaemia
- Elevated creatiine kinase (CK)
- Elevated LDH
- Elevated triglycerides
Inflammatory markers
Elevation of inflammatory markers like ESR, C reactive protein, procalcitonin, IL-6, IL-12, d-dimer, ferritin is seen in HIV patients co-infected with HIV[4]
X-ray
Xray of patients with HIV co-infected with COVID-19 may show[4]
- Consolidation
- Interstitial pulmonary infiltrates
- Bilateral pulmonary infiltrates
Treatment
Medical Therapy
- Treatment of COVID-19 patients with HIV is similar to current guidelines of treatment of general population with COVID-19 along with current maintenance of their antiretroviral therapy. No specific antretroviral therapy has been found effective against SARS-CoV-2 virus. Following treatment have been used in HIV individuals with COVID-19 infection.
- Supportive care-Patients with HIV who develop mild COVID-19 illness could be treated with supportive care with symptomatic relief at home. They should continue their antiretroviral therapy. [10]
- In case of moderate to severe COVID-19 infection they might need to be hospitalized. ART therapy should be continued when hospitalized.
- Llopinavir–ritonavir- It inhibits the activity of the HIV-1 protease. Clinical trial found that treatment with lopinavir–ritonavir was not associated with clinical improvement in COVID-19 patients.[4][10][21]
- Tocilizumab -which is a monoclonal antibody which binds to interleukin-6,. It has been used in patients with HIV who develop COVID-19. A retrospective study found it effective in reducing nortalility in severe COVID-19 patients [4]
- Darunavir- It has been used in HIV SARS-CoV-2 coinfected individuals as part of their continued anti retroviral therapy. Trial has found no benefit in COVID-19 patients.[4]
- Antibiotics such as azithromycin have been used inHIV SARS-CoV-2 coinfected individuals. [4]
- Patients who are taking investigational ARV medication as part of their regimen, should be continued on the same medication if possible.[10]
- Patients who have underlying medical conditions should be managed accordingly to prevent complications of COVID-19 infection.
| COVID-19 treatment |
|---|
| interferon beta -1b |
| hydroxychloroquine(77%) |
| antibiotics(49%) |
| corticosteroids(38%) |
| tocilizumab(10%) |
| Ritonavir based lopinavir(36%) |
| Darunavir(21%) |
Recommendations for Patients with HIV
- Maintain the supply for antiretroviral therapy for a minimum of 30 days and ideal supply for 90 days.[10]
- People with suppressed HIV viral load and in stable health, should postpone their routine medical care and laboratory visits to the extent possible.[10]Virtual visit and telemedicine should be considered for non-urgent care and non-adherence counseling[10]
- Whenever possible their order for medications should be delivered at home to avoid the exposure.
- If they develop symptoms of COVID-19 like fever, cough, shortness of breath, etc they should seek medical advice.[10]
- They should make sure their vaccination status is updated. Influenza and pneumococcal vaccinations should be kept up to date.[10]
- Switching of the antiretroviral therapy should be delayed until close follow up monitoring is possible. No antiretroviral therapy has been found effective for treatment or prevention of COVID-19. Therefore, their Antiretroviral therapy should not be switched for the purpose of prevention of COVID-19 infection.[10]
- If the HIV patient has been quarantined or self isolated due to exposure to SARS-CoV-2, it should be ensured that they have adequate antiretroviral therapy and additional drug refills should be expedited as needed.[10]
- HIV individuals should follow the standard precautions of hand sanitizing, social distancing, covering face with face masks whenever they have to go out in public places or clinics.[10]
References
- ↑ "WHO. HIV/AIDS data and statistics".
- ↑ "Information from CDC on HIV/AIDS".
- ↑ Zhu, Feng; Cao, Yang; Xu, Shuyun; Zhou, Min (2020). "Co‐infection of SARS‐CoV‐2 and HIV in a patient in Wuhan city, China". Journal of Medical Virology. 92 (6): 529–530. doi:10.1002/jmv.25732. ISSN 0146-6615.
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 "Interim Guidance for COVID-19 and Persons with HIV".
- ↑ Blanco, Jose L; Ambrosioni, Juan; Garcia, Felipe; Martínez, Esteban; Soriano, Alex; Mallolas, Josep; Miro, Jose M (2020). "COVID-19 in patients with HIV: clinical case series". The Lancet HIV. 7 (5): e314–e316. doi:10.1016/S2352-3018(20)30111-9. ISSN 2352-3018.
- ↑ 6.0 6.1 Vizcarra, Pilar; Pérez-Elías, María J; Quereda, Carmen; Moreno, Ana; Vivancos, María J; Dronda, Fernando; Casado, José L; Moreno, Santiago; Pérez-Elías, Maria Jesús; Fortún, Jesús; Navas, Enrique; Quereda, Carmen; Dronda, Fernando; Del Campo, Santos; López-Vélez, Rogelio; Cobo Reinoso, Javier; Casado, José Luis; Moreno, Ana; Norman, Franceca; Martín-Dávila, Pilar; Hermida, José Manuel; Pérez Molina, José Antonio; Monge, Begoña; Pintado, Vicente; Serrano-Villar, Sergio; Sánchez-Conde, Matilde; Chamorro, Sandra; Escudero, Rosa; Gioia, Francesca; Comeche, Belén; Crespillo, Clara; Herrera, Sabina; Ron, Raquel; Martínez-Sanz, Javier; Pons-Guillén, Mario; Vivancos, María Jesús; Vizcarra, Pilar (2020). "Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort". The Lancet HIV. doi:10.1016/S2352-3018(20)30164-8. ISSN 2352-3018.
- ↑ Ziegler, Carly G.K.; Allon, Samuel J.; Nyquist, Sarah K.; Mbano, Ian M.; Miao, Vincent N.; Tzouanas, Constantine N.; Cao, Yuming; Yousif, Ashraf S.; Bals, Julia; Hauser, Blake M.; Feldman, Jared; Muus, Christoph; Wadsworth, Marc H.; Kazer, Samuel W.; Hughes, Travis K.; Doran, Benjamin; Gatter, G. James; Vukovic, Marko; Taliaferro, Faith; Mead, Benjamin E.; Guo, Zhiru; Wang, Jennifer P.; Gras, Delphine; Plaisant, Magali; Ansari, Meshal; Angelidis, Ilias; Adler, Heiko; Sucre, Jennifer M.S.; Taylor, Chase J.; Lin, Brian; Waghray, Avinash; Mitsialis, Vanessa; Dwyer, Daniel F.; Buchheit, Kathleen M.; Boyce, Joshua A.; Barrett, Nora A.; Laidlaw, Tanya M.; Carroll, Shaina L.; Colonna, Lucrezia; Tkachev, Victor; Peterson, Christopher W.; Yu, Alison; Zheng, Hengqi Betty; Gideon, Hannah P.; Winchell, Caylin G.; Lin, Philana Ling; Bingle, Colin D.; Snapper, Scott B.; Kropski, Jonathan A.; Theis, Fabian J.; Schiller, Herbert B.; Zaragosi, Laure-Emmanuelle; Barbry, Pascal; Leslie, Alasdair; Kiem, Hans-Peter; Flynn, JoAnne L.; Fortune, Sarah M.; Berger, Bonnie; Finberg, Robert W.; Kean, Leslie S.; Garber, Manuel; Schmidt, Aaron G.; Lingwood, Daniel; Shalek, Alex K.; Ordovas-Montanes, Jose; Banovich, Nicholas; Barbry, Pascal; Brazma, Alvis; Desai, Tushar; Duong, Thu Elizabeth; Eickelberg, Oliver; Falk, Christine; Farzan, Michael; Glass, Ian; Haniffa, Muzlifah; Horvath, Peter; Hung, Deborah; Kaminski, Naftali; Krasnow, Mark; Kropski, Jonathan A.; Kuhnemund, Malte; Lafyatis, Robert; Lee, Haeock; Leroy, Sylvie; Linnarson, Sten; Lundeberg, Joakim; Meyer, Kerstin; Misharin, Alexander; Nawijn, Martijn; Nikolic, Marko Z.; Ordovas-Montanes, Jose; Pe’er, Dana; Powell, Joseph; Quake, Stephen; Rajagopal, Jay; Tata, Purushothama Rao; Rawlins, Emma L.; Regev, Aviv; Reyfman, Paul A.; Rojas, Mauricio; Rosen, Orit; Saeb-Parsy, Kourosh; Samakovlis, Christos; Schiller, Herbert; Schultze, Joachim L.; Seibold, Max A.; Shalek, Alex K.; Shepherd, Douglas; Spence, Jason; Spira, Avrum; Sun, Xin; Teichmann, Sarah; Theis, Fabian; Tsankov, Alexander; van den Berge, Maarten; von Papen, Michael; Whitsett, Jeffrey; Xavier, Ramnik; Xu, Yan; Zaragosi, Laure-Emmanuelle; Zhang, Kun (2020). "SARS-CoV-2 Receptor ACE2 Is an Interferon-Stimulated Gene in Human Airway Epithelial Cells and Is Detected in Specific Cell Subsets across Tissues". Cell. 181 (5): 1016–1035.e19. doi:10.1016/j.cell.2020.04.035. ISSN 0092-8674.
- ↑ 8.0 8.1
- ↑ 9.0 9.1 "Society for Maternal-Fetal Medicine, Dotters-Katz S, Hughes BL. Coronavirus (COVID-19) and Pregnancy: What Maternal-Fetal Medicine Subspecialists Need to Know. 2020" (PDF).
- ↑ 10.00 10.01 10.02 10.03 10.04 10.05 10.06 10.07 10.08 10.09 10.10 10.11 10.12 "Interim Guidance for COVID-19 and Persons with HIV".
- ↑ Siston, Alicia M. (2010). "Pandemic 2009 Influenza A(H1N1) Virus Illness Among Pregnant Women in the United States". JAMA. 303 (15): 1517. doi:10.1001/jama.2010.479. ISSN 0098-7484.
- ↑ Alfaraj, Sarah H.; Al-Tawfiq, Jaffar A.; Memish, Ziad A. (2019). "Middle East Respiratory Syndrome Coronavirus (MERS-CoV) infection during pregnancy: Report of two cases & review of the literature". Journal of Microbiology, Immunology and Infection. 52 (3): 501–503. doi:10.1016/j.jmii.2018.04.005. ISSN 1684-1182.
- ↑ Wong, Shell F; Chow, Kam M; Leung, Tse N; Ng, Wai F; Ng, Tak K; Shek, Chi C; Ng, Pak C; Lam, Pansy W.Y; Ho, Lau C; To, William W.K; Lai, Sik T; Yan, Wing W; Tan, Peggy Y.H (2004). "Pregnancy and perinatal outcomes of women with severe acute respiratory syndrome". American Journal of Obstetrics and Gynecology. 191 (1): 292–297. doi:10.1016/j.ajog.2003.11.019. ISSN 0002-9378.
- ↑ "Interim Guidance for COVID-19 and Persons with HIV".
- ↑ Chen, Huijun; Guo, Juanjuan; Wang, Chen; Luo, Fan; Yu, Xuechen; Zhang, Wei; Li, Jiafu; Zhao, Dongchi; Xu, Dan; Gong, Qing; Liao, Jing; Yang, Huixia; Hou, Wei; Zhang, Yuanzhen (2020). "Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records". The Lancet. 395 (10226): 809–815. doi:10.1016/S0140-6736(20)30360-3. ISSN 0140-6736.
- ↑ Wang, Dawei; Hu, Bo; Hu, Chang; Zhu, Fangfang; Liu, Xing; Zhang, Jing; Wang, Binbin; Xiang, Hui; Cheng, Zhenshun; Xiong, Yong; Zhao, Yan; Li, Yirong; Wang, Xinghuan; Peng, Zhiyong (2020). "Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus–Infected Pneumonia in Wuhan, China". JAMA. 323 (11): 1061. doi:10.1001/jama.2020.1585. ISSN 0098-7484.
- ↑ Feng, Ling; Zhang, Jingyi; Cao, Yong; Liu, Weiyong; Chen, Ling; Guo, Lili; Wang, Shaoshuai (2020). "A Case Report of Neonatal 2019 Coronavirus Disease in China". Clinical Infectious Diseases. doi:10.1093/cid/ciaa225. ISSN 1058-4838.
- ↑ Shiau, Stephanie; Krause, Kristen D.; Valera, Pamela; Swaminathan, Shobha; Halkitis, Perry N. (2020). "The Burden of COVID-19 in People Living with HIV: A Syndemic Perspective". AIDS and Behavior. doi:10.1007/s10461-020-02871-9. ISSN 1090-7165.
- ↑ Kucirka, Lauren; et al. (May 13, 2020). "Variation in False-Negative Rate of Reverse Transcriptase Polymerase Chain Reaction–Based SARS-CoV-2 Tests by Time Since Exposure". acp journals. Retrieved July 11, 2020.
- ↑ "What is the diagnostic accuracy of antibody tests for the detection of infection with the COVID-19 virus?".
- ↑ Cao, Bin; Wang, Yeming; Wen, Danning; Liu, Wen; Wang, Jingli; Fan, Guohui; Ruan, Lianguo; Song, Bin; Cai, Yanping; Wei, Ming; Li, Xingwang; Xia, Jiaan; Chen, Nanshan; Xiang, Jie; Yu, Ting; Bai, Tao; Xie, Xuelei; Zhang, Li; Li, Caihong; Yuan, Ye; Chen, Hua; Li, Huadong; Huang, Hanping; Tu, Shengjing; Gong, Fengyun; Liu, Ying; Wei, Yuan; Dong, Chongya; Zhou, Fei; Gu, Xiaoying; Xu, Jiuyang; Liu, Zhibo; Zhang, Yi; Li, Hui; Shang, Lianhan; Wang, Ke; Li, Kunxia; Zhou, Xia; Dong, Xuan; Qu, Zhaohui; Lu, Sixia; Hu, Xujuan; Ruan, Shunan; Luo, Shanshan; Wu, Jing; Peng, Lu; Cheng, Fang; Pan, Lihong; Zou, Jun; Jia, Chunmin; Wang, Juan; Liu, Xia; Wang, Shuzhen; Wu, Xudong; Ge, Qin; He, Jing; Zhan, Haiyan; Qiu, Fang; Guo, Li; Huang, Chaolin; Jaki, Thomas; Hayden, Frederick G.; Horby, Peter W.; Zhang, Dingyu; Wang, Chen (2020). "A Trial of Lopinavir–Ritonavir in Adults Hospitalized with Severe Covid-19". New England Journal of Medicine. 382 (19): 1787–1799. doi:10.1056/NEJMoa2001282. ISSN 0028-4793.