Full Text Article

Clinical Features and Outcomes of COVID-19 in People Living with HIV: A Single-Center, Age-Matched Cohort Study of Hospitalized and Clinic Patients

Received Date: February 06, 2021 Accepted Date: March 06, 2021 Published Date: March 08, 2021

doi: 10.17303/jaid.2021.8.102

Citation: Rajendraprasad Sanu S (2021) Clinical Features and Outcomes of COVID-19 in People Living with HIV: A Single-Center, Age-Matched Cohort Study of Hospitalized and Clinic Patients. J HIV AIDS Infect Dis 8: 1-9.

As we continue to learn the effects of the human immunodeficiency virus-infected with SARS-CoV-2. We describe 7 patients with an age-matched cohort in hospitalized and clinic patients in our hospital health system with a 90 day follow up for these patients. A retrospective, age-matched cohort study with people living with HIV (PWLH) that were diagnosed with COVID‐19 in the hospital and on an outpatient basis at our health system. Duration of symptoms in PLWH was noted to be longer (6-49 days); they also had a close follow-up with their primary care physician. PLWH noted to have respiratory symptoms (air hunger, shortness of breath, and productive cough) for a duration of 1-2 months after COVID-19 testing. This case series does not show an increased risk of infection or adverse outcomes in COVID‐19 infection when compared with the general population consistent with prior case series. The persistence of respiratory symptoms in PLWH for up to 2 months warrants further research.

Keywords: COVID-19; HIV infection; SARS-CoV-2; Antiretroviral therapy; Follow-up

List of Abbreviations: SARS-CoV-2: Severe Acute Respiratory Syndrome Coronavirus 2; HIV: Human Immunodeficiency Virus; PWLH: People Living With HIV; COVID‐19: Coronavirus Disease 2019; CD4: Cluster of Differentiation 4 CD4+ T Helper Cells; ART: Antiretroviral Therapy; RT‐PCR: Reverse Transcription- Polymerase Chain Reaction; CDC: Centers for Disease Control and Prevention; CHI: Catholic Health Initiatives; PCR: Polymerase Chain Reaction; IRB: Institutional Review Board; EMR: Electronic Medical Record; CABP: Community-Acquired Bacterial Pneumonia; RNA: Ribonucleic Acid

The 2019 novel coronavirus (SARS-CoV-2) causing COVID-19 infection has emerged to become a global pandemic with significant fatality. Studies have demonstrated that older adults and people of any age who have serious underlying medical condition might be at higher risk for severe illness, including people who are immunocompromised [1]. Contrary to the presumption, studies showed that people living with HIV (PLWH) are not at higher risk of contracting COVID-19 compared to those without a diagnosis of HIV [2-8]. The reported incidence of COVID-19 in PLWH in various studies from China, the United Kingdom, and New York City was low at 0.8% to 1% [9-11].

The risk for people coinfected with COVID-19 and HIV experiencing severe illness was reported to be greatest in PLWH with a low CD4 cell count, and not receiving antiretroviral therapy (ART) [12-14]. On the other hand, the severity of COVID-19 pneumonia/disease in PLWH was similar to the general population [15]. The proposed hypothesis includes a protective effect of ART, immune exhaustion, or defective cellular immunity that prevents the cytokine storm known to create severe illness in those infected with COVID-19.

As we continue to learn about the COVID-19 pandemic and its effects on the HIV community there have been several case reports and case series which evaluated hospitalized patients with SARS-CoV-2 infection in PLWH. We performed a retrospective, age-matched cohort study with PWLH that were diagnosed with COVID‐19 confirmed by a positive SARS‐CoV‐2 RT‐PCR test from nasopharyngeal swab specimens that were treated in the hospital and on an outpatient basis at our health system. At present, the CDC states that “based on limited data, we believe people with HIV who are on effective HIV treatment have the same risk for COVID-19 as people who do not have HIV.”

A retrospective, age-matched cohort study with PWLH that were diagnosed with COVID‐19 in the hospital and on an outpatient basis at our CHI health system in Omaha, Nebraska. Two providers that care for HIV patients that were alerted to patients with positive COVID-19 PCR testing those that were admitted to a CHI hospital or obtained a COVID-19 PCR test on out patient basis. Patients age 19-95 years who have tested positive for COVID-19 in the CHI Health system from April 1, 2020-July 31, 2020 were eligible for electronic medical record (EMR) review. EMR was used to evaluate follow up with any medical provider with in 90 days from first positive COVID-19 PCR test. After all patient information was gathered and entered into the excel spreadsheet, the spreadsheet was locked as per institutional IRB recommendations.

PLWH contracting COVID-19 with a comparative age and sex control group found several important findings. (Table 1a) Of the 7 PLWH, only 2/7 patients were noted to have a CD4 count of < 200 cells/mm3, of which only one patient had a detectable viral load on ART [15]. Patients with HIV that were hospitalized received more antibiotics with broader coverage (vancomycin with piperacillin-tazobactam) compared to ceftriaxone with azithromycin and for longer duration when compared to those that did not have HIV for presumed community-acquired bacterial pneumonia (CABP).

Duration of symptoms in PLWH was noted to be longer (range of 6-49 days). It is unclear if this is due to COVID-19 infection alone. Symptoms in PLWH were dramatically longer compared to the control cohort (Table 1b), with symptom duration range in the control cohort of 1-10 days. In the immunocompetent host, SARS-CoV-2 could present as an asymptomatic infection with mild symptoms all the way to severe disease, with the resolution of the infection within 1–3 weeks after the onset of symptoms [16]. Immunocompromised patients may harbor the infection for a longer duration up to 9 weeks [17]. Unfortunately, due to limitations in testing and inconsistent follow up we were not able to obtain a negative test in all patients. Only 4/14 patients from both cohorts underwent repeat SARS-CoV-2 testing, with only one HIV patient getting tested 5 months out from the initial diagnosis.

PLWH did appear to get closer follow up with their primary care physician. Thirty,60, and 90 days follow up for PLWH found to have respiratory symptoms (air hunger, shortness of breath, and productive cough) for a duration of 1-2 months after COVID-19 testing. Carfì, et al. found fatigue and dyspnea up to 60 days after diagnosis in patients recovering from COVID-19 [18]. Fortunately, no PLWH required admission to the hospital. Interesting to note that the control group did not have the same level of follow-up or did not appear to have accessed our health care system for any further respiratory complaints. Unclear if respiratory symptoms persist in PLWH for a longer duration due to HIV.

The majority of control patients displayed mild COVID-19 disease, and 2/7 PLWH patients had moderate or moderate/severe illness. Fever/elevated temperature over 100 F was noted in 3/7 of PLWH. Other studies show a similar presentation in PLWH with COVID-19, with fever as a common symptom [2,4,8,22,23]. Partner exposure in 2/7 was noted to be the primary COVID-19 exposure in PLWH while 5/7 acquired it from work/community in the control group.

Forty three percent of PLWH were receiving bictegravir, emtricitabine & tenofovir alafenamide (BIC/FTC/TAF), 29% received elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (EVG/COBI/FTC/TAF), 14% received emtricitabine & tenofovir alafenamide (FTC/TAF), with dolutegravir (DTG) and 14% received abacavir, lamivudine, dolutegravir (ABC/DTG /3TC). Only one patient-patient#4 in HIV group did not have TAF in their ART regimen and was noted to be the only moderate to severe case of COVID-19. This patient required intravenous methylprednisolone and oral prednisone with progressive acute respiratory failure with an oxygen requirement of 2 liters of oxygen on discharge after a 6-day hospitalization.

This patient was hospitalized early in the pandemic and also received hydroxychloroquine and broad-spectrum antibiotics. This was the longest hospitalization and most severe case despite undetectable viral load but a CD4 count of 29/uL. The low CD4 count, likely could be responsible for the severity of symptoms [21]. Type 2 diabetes mellitus and moderate persistent asthma also placed the patient at higher risk. Tenofovir blocks the critical RNA-dependent RNA polymerase of SARS-CoV-2, and it is structurally related to remdesivir thus possibly providing a protective effect [5,21,22]. Several studies note a protective effect of immunosuppression although most patients have been on ART and appear to be well-controlled with a similar outcome as patients without HIV.

In PLWH, reported studies show little difference in hospitalized outcome for COVID-19 [2,5,6,8,19,25-27]. Only 2 studies (Suwanwongse, et al. and Boulle et al.) demonstrated worsening mortality in this population [28,29]. Taking into account the racial and gender disparities, comorbidities, and lower socio-economic background likely contributed to the worsening mortality in these two studies [30].

As with previous case series, there are several limitations. First, this was a small retrospective and case-controlled series with inpatient and outpatient cases that were identified only after having symptoms. Second, laboratory information was not obtained from those that were treated on an outpatient basis. Third, the follow-up information was obtained on review of the patient’s medical records, thus the severity or exact duration of symptoms is not available especially in the control group.

In conclusion, PLWH does not appear to have an increased risk of infection or adverse outcomes in COVID‐19 infection when compared with the general population. While partner exposure was noted to be the primary cause of contracting COVID-19 while the age-matched cohort appeared to be from the community. The protective effect of tenofovir also warrants further evaluation. In our case series, PWLH and COVID-19 were noted to have symptoms that last for up to 2 months whether this is protective or detrimental is difficult to interpret at present, and warrants further research.

  1. Guan WJ, Ni ZY, Hu Y (2020) Clinical Characteristics of Coronavirus Disease 2019 in China. N Engl J Med 382: 1708-20.
  2. Blanco JL, Ambrosioni J, Garcia F (2020) COVID-19 in patients with HIV: clinical case series. Lancet HIV 7: e314-6.
  3. Louisa SJ, Lin Serene WX, Gollamudi S (2020) A case of HIV and SARS‐CoV‐ 2 co‐infection in Singapore. J Acquir Immune Defic Syndr 84: e23‐4.
  4. Zhu F, Cao Y, Xu S, Zhou M (2020) Co-infection of SARS-CoV-2 and HIV in a patient in Wuhan city, China. J Med Virol 92: 529-30.
  5. Gervasoni C, Meraviglia P, Riva A (2020) Clinical features and outcomes of HIV patients with coronavirus disease 2019 [published online ahead of print, 2020 May 14]. Clin Infect Dis 2020: ciaa579.
  6. Härter G, Spinner CD, Roider J (2020) COVID-19 in people living with human immunodeficiency virus: a case series of 33 patients. Infection 48: 681-6.
  7. Altuntas Aydin O, Kumbasar Karaosmanoglu H, Kart Yasar K (2020) HIV/SARS-CoV-2 coinfected patients in Istanbul, Turkey. J Med Virol 92: 2288-90.
  8. Wu Q, Chen T, Zhang H (2020) Recovery from COVID-19 in two patients with coexisted HIV infection. J med virology.
  9. Wang D, Hu B, Hu C (2020) Clinical Characteristics of 138 Hospitalized Patients With 2019 Novel Coronavirus-Infected Pneumonia in Wuhan, China. JAMA 323: 1061-9.
  10. Docherty AB, Harrison EM, Green CA (2020) Features of 16,749 hospitalised UK patients with COVID-19 using the ISARIC WHO clinical characterization protocol. medRxiv preprint
  11. Richardson S, Hirsch JS, Narasimhan M (2020) Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area JAMA.
  12. Prevention CDC (2020) COVID-19 and HIV 2020.
  13. National Center for Immunization and Respiratory Diseases (NCIRD) DoVD.COVID-19. People with HIV 2020.
  14. EACS. EACS & BHIVA Statement on risk of COVID-19 for people living with HIV(PLWH) 2020.
  15. Qasim A, Mansour M, Kousa O, Awad D, Abuhazeem B (2020) A case of coronavirus disease 2019 in acquired immunodeficiency syndrome patient: a case report and review of the literature. Intractable Rare Dis Res 9: 256-9.
  16. Chang D, Mo G, Yuan X (2020) Time Kinetics of Viral Clearance and Resolution of Symptoms in Novel Coronavirus Infection. Am J Respir Crit Care Med 201: 1150-2.
  17. Helleberg M, Niemann CU, Moestrup KS (2020) Persistent COVID-19 in an Immunocompromised Patient Temporarily Responsive to Two Courses of Remdesivir Therapy. J Infect Dis 222: 1103-7.
  18. Carfì A, Bernabei R, Landi F (2020) Gemelli Against COVID-19 Post-Acute Care Study Group. Persistent Symptoms in Patients After Acute COVID-19. JAMA 324: 603-5.
  19. Ruan L, Zhang Y, Luo Y, et al. Clinical features and outcomes of four HIV patients with COVID-19 in Wuhan, China [published online ahead of print, 2020 Jun 25]. J Med Virol. 2020;10.1002/jmv.26223.
  20. Wang M, Luo L, Bu H, Xia H (2019) 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 96: 148-50.
  21. Elfiky AA (2020) Ribavirin, Remdesivir, Sofosbuvir, Galidesivir, and Tenofovir against SARS-CoV-2 RNA dependent RNA polymerase (RdRp): A molecular docking study. Life Sci 253: 117592.
  22. Qin C, Zhou L, Hu Z (2020) Dysregulation of Immune Response in Patients With Coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis 71: 762-8.
  23. Ridgway JP, Farley B, Benoit JL (2020) A Case Series of Five People Living with HIV Hospitalized with COVID-19 in Chicago, Illinois. AIDS Patient Care STDS 34: 331-5.
  24. Karmen-Tuohy S, Carlucci PM, Zervou FN (2020) Outcomes Among HIV-Positive Patients Hospitalized With COVID-19. J Acquir Immune Defic Syndr 85: 6-10.
  25. Siegel K, Swartz T, Golden E (2020) Covid-19 and People with HIV Infection: Outcomes for Hospitalized Patients in New York City. Clinical Infectious Diseases.
  26. Shalev N, Scherer M, LaSota ED (2020) Clinical characteristics and outcomes in people living with HIV hospitalized for COVID-19. Clin Infect Dis 2020: ciaa635.
  27. Vizcarra P, Pérez-Elías MJ, Quereda C (2020) Description of COVID-19 in HIV-infected individuals: a single-centre, prospective cohort Lancet HIV S2352-3018: 30164-8.
  28. Suwanwongse K, Shabarek N (2020) Clinical features and outcome of HIV/SARS-CoV-2 coinfected patients in The Bronx, New York city. J Med Virol 2020.
  29. Boulle A, Davies MA, Hussey H (2020) Risk factors for COVID-19 death in a population cohort study from the Western Cape Province, South Africa Clin Infect Dis 2020: ciaa1198.
  30. Kopel J, Perisetti A, Roghani A, Aziz M, Gajendran M, et al. (2020) Racial and Gender-Based Differences in COVID-19. Front Public Health 8: 418.
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