key: cord-1013130-779g8tr1
authors: Khaba, Moshawa Calvin; Ngale, Tshepo Cletus; Madala, Nomandla
title: COVID-19 in an HIV-infected patient. Lessons learned from an autopsy case
date: 2020-09-25
journal: Int J Infect Dis
DOI: 10.1016/j.ijid.2020.09.1435
sha: f1f93e819aaf5c171a9eccfae9b4535361b4dfad
doc_id: 1013130
cord_uid: 779g8tr1

Despite measures put in places to curb the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across South Africa, there has been a rapid spread which caused extensive morbidity and mortality. Whilst there is currently increased COVID-19 associated death, autopsies on COVID positive individuals are not routinely performed. An autopsy was performed on a 19 years old African patient who was recently diagnosed with human immunodeficiency virus (HIV). He presented with clinical features of SARS-CoV-2 which subsequently tested positive for. Important histopathological findings included diffuse alveolar damage and fibrin thrombi. No superimposed infections were noted. The cause of death was attributed to COVID-19. We report the first autopsy case of HIV-infected individual with COVID-19 as the cause of death.

The first confirmed case of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was reported in China in December 2019. This viral infection has since spread across the globe with the first case reported in South Africa on March 20, 2020.

Coronaviruses are enveloped, non-segmented, positive-sense single-stranded RNA viruses. The other two that are known to cause human diseases are beta coronaviruses-severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) (1, 2) .

The clinical features ranges from asymptomatic to mild symptoms such as cough, fever, dyspnoea and severe disease which leads to acute respiratory distress syndrome and death (1, 3) . Older patients and individual with hypertension, diabetes and cancer are at increased risk of infection (3) . There is little knowledge on HIV/AIDS and its impact on the clinical outcomes in patients with . To the best of our knowledge, this manuscript represents the first published report of an autopsy performed on an HIV infected patient with cause of death attributed to COVID-19.

Clinical features 19 years old male African patient who was referred from a local clinic with one-week history of generalised weakness, fatigue, cough and shortness of breath. He was recently diagnosed with human immunodeficiency virus (HIV) with CD4 T lymphocytes of 17 cell/uL and viral load of 1487946 copies/mL. He was not yet on anti-retroviral therapy (ART). He had no other co-morbidities. On examination, his blood pressure was 95/33 mmHg, heart rate of 103 beats/minute, fever of 38,7 0 C and saturation of 95% on 40% oxygen. He was confused, pale and hypovalaemic with generalised lymphadenopathy.

He had bilateral crackles on chest examination. Abdominal examination revealed massive splenomegaly and hepatomegaly.

He was given an intravenous stat dose of ceftriaxone and acetaminophen; and admitted to a patient under investigation (PUI) ward for COVID-19 suspects. The chest x-ray showed extensive bilateral infiltrates (Fig. 1a) . The full blood count showed bicytopaenia with low haemoglobin and platelets of 100 x 10 9 /L; and transfused 3 units of red blood cells. The liver function tests were mildly deranged. C-reactive protein, ferritin and procalcitonin were raised. The renal function tests revealed pre-renal acute kidney injury most likely secondary to the hypovolaemia (see table 1 for investigations). Despite SARS-Cov-2 infection, in view of the retroviral disease, pneumocystis pneumonia, bacterial pneumonia and tuberculosis could not be excluded. He was started on trimethoprim-sulfamethoxazole 1920mg 6hourly, hydrocortisone 200mg 8 hourly, azithromycin 500mg daily and enoxaparin 60mg daily. Polymerase chain reaction of the nasopharyngeal swab detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Three days post admission, his confusion worsened; developed cardiorespiratory failure and died.

A complete autopsy was performed in a negative pressure autopsy room with personal protective equipment (PPE), including N95 masks, eye protection, gloves and gowns.

The patient's body mass index was 18.1 kg/m 2 . He was emaciated, hypovolaemic and pale with generalized lymphadenopathy. He had serosanguineous bilateral pleural effusion and ascites. The right and left lungs weighed 884g and 772g (n=360 -570g and 325 -480g) respectively. They were oedematous, firm with alternating pale and red areas (Fig. 2b) . The spleen weighed 1310g (n=156) with haemorrhagic cut surface. The liver weighed 2400g (n= 1500 -1800) with pale, greasy and yellowish cut surface. The kidneys had smooth surface with good corticomedullary differentiation on cut section. The brain and heart were unremarkable. The bone marrow was pale and soft.

Microscopic features: Sections of the lungs showed extensive oedema with bilateral diffuse alveolar damage (DAD) evidenced by hyaline membrane formation (Fig 1c-e) . Adjacent small calibre blood vessels with fibrin thrombi were noted (Fig 1f) . Granulomatous inflammation or infectious pathogens were not seen. The spleen was poorly preserved; however, infectious pathogens or neoplastic infiltrate were not seen. Sections of the liver showed microvesicular steatosis and lobular inflammation. The heart, brain and bone marrow were unremarkable. The kidney, lymph nodes and pancreas were poorly preserved. The well preserved glomeruli did not show features of hypertension, diabetes mellitus or HIV associated nephropathy. Furthermore, fibrin thrombi were not seen within the glomerular capillaries.

The final cause of death was SARS-CoV-2 (COVID-19) infection in HIV infected patient.

Much as performing autopsies on COVID-19 positive individuals is still not routinely perfomed due to safety reasons, there has been a recent increase in COVID-19 autopsy. The spectrum of pathological findings has emerged from this.

The most consistently described autopsy findings are diffuse alveolar damage with associated desquamation of pneumocytes, oedema and capillary congestion (1). Increased intra-alveolar macrophage and enlarged, atypical pneumocytes have also been seen in advanced disease (4).

Vascular microthrombi are seen in areas of diffuse alveolar damage with diffuse endothelial damage. Whilst this feature is not pathognomonic for COVID-19, it has been postulated to be specific to COVID-19 as this is not a normal finding in DAD (4,5). Luca Carsana et al. found that fibrin thrombi of small vessels were observed in 87% of lung cases and high levels of D-dimers in the blood (1)

Elevated D-dimers is associated increased thrombin generation in COVID-19 (6) . The existence of fibrin thrombi and high serum levels of D-dimers may explain the severe hypoxaemia that indicate acute respiratory distress syndrome in these patients (1) . D-dimer levels of >1 μg/mL is associated with increased mortality in COVID-19 patients (6) .

In accord to what is already published, the lung findings on the index patient showed early phase of diffuse alveolar damage with associated microthrombi which is seen in COVID-19. The lung findings on this patient was not different from the ones reported on non-HIV infected patient. Little is known of the interaction between HIV infection and SARS-CoV-2 pathogenesis. Furthermore, there's little knowledge on the impact of HIV infection on the clinical outcomes of patients infected with SARS-CoV-2. Whilst HIV infected people on treatment with normal CD4 count and low viral load may not be at a high risk of serious illness, the presence of other chronic conditions may increase their overall risk (7) The fact that SARS-CoV-2 can cause transient immune deficiency, it denotes that HIV and COVID-19 interaction may have adverse immunological and clinical outcomes. Therefore, defective cellular immunity in HIV infected patients may be paradoxically protective for severe cytokine dysregulation in patients with COVID-19 (8) . The index patient's clinical emaciation suggests that the low CD4 count was pre-COVID-19.

Shalev et al hypothesized that the absence of T-cell activation alleviates the severe immunopathological phenomena seen in COVID-19. While his study had its limitation, he further suggested that SARS-CoV-2 does not act as an opportunistic pathogen in patients with uncontrolled HIV or AIDS (3).

Tuohy et al suggested that HIV status did not significantly impact clinical outcomes in patients with SARS-CoV-2 infection, albeit he detected trends suggestive of worse course outcome in HIV-positive patients (9) .

Although the index patient was HIV infected, he was young without comorbidities. He had lymphopaenia and was not yet on antiretroviral therapy. This is contrary to the few published cases which show that high mortality rate of COVID-19 in HIV infected patients is usually associated with older patients (> 50 years) with diabetes, hypertension, etc. Furthermore, in view of the index patient's low CD4 count, secondary or opportunistic infection such as tuberculosis, pneumocystis pneumonia or cryptoccocal infection would be expected. However, there was no superimposed infection identified on lung sections examined. This further favoured COVID-19 as the sole cause of death in this patient.

With its own limitation, this autopsy has not shown any distinct pathological findings specific to HIV infection in contrast to what is already described in non-HIV infected patients. In lieu of this, more studies regarding HIV and COVID-19 association are warranted as typical clinicopathological findings may likely have important treatment implications for these patients.

The autopsy was done seven days after he demised, awaiting a written informed consent from the family. Hence some of the organs were autolysed.

MCK, TCN and NM conceptualised the report and wrote the manuscript. All authors have read and approved the submitted version of this manuscript.

All materials and data described in this manuscript are available upon reasonable request to the corresponding author, and if complying with patients' privacy.

Written informed consent was obtained from the patients' parents for scientific publication of this case report.

Sefako Makgatho Health Sciences University Research Ethics Committee (SMUREC) approved the publication of these case series. SMUREC/M/215/2020

No funding was secured for this study.

The authors declare that they have no conflicts of interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Legends   Fig 1: a , chest x-ray shows extensive bilateral infiltrates with left pleural effusion; b, firm lung with alternating red and pale areas, and oedema. No visible thrombus; c -e, diffuse alveolar damage with hyaline membrane formation ( ); f, Small vessels with fibrin thrombi ( ).

J o u r n a l P r e -p r o o f

Articles Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy : a two-centre descriptive study

Clinical Characteristics and Outcomes in People Living With Human Immunodeficiency Virus Hospitalized for Coronavirus Disease

Articles Pulmonary and cardiac pathology in African American patients with COVID-19 : an autopsy series from New Orleans

Articles Histopathology and ultrastructural findings of fatal COVID-19 infections in Washington State : a case series

Hematologic parameters in patients with COVID-19 infection

Clinical features and outcomes of HIV patients with coronavirus disease 2019

COVID -19 in people living with human immunodeficiency virus : a case series of 33 patients

Outcomes Among HIV-Positive Patients Hospitalized With COVID-19

We thank Ms B Ngubeni and NHLS management for motivation and support all research endeavours.

J o u r n a l P r e -p r o o f