Background
An outbreak of pneumonia of unknown origin was first reported in Wuhan, China in December 2019. The cause had been identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was officially named as COVID-19 (coronavirus disease 2019) by World Health Organization (WHO), could induce symptoms including fever, dry cough, dyspnea, fatigue, and lymphopenia and ground-glass lung changes in radiology in infected patients. The pandemic of COVID-19 has posed great threat to public health across the globe. Until April 21, 2020, 2,397,217 cases were confirmed globally, including 84,250 cases in China [1]. A total of 162,956 patients have died from this viral infection [2]. Severe cases developed life-threatening complications, such as respiratory failure, shock, and multiple organs dysfunction [3]. We report co-infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and HIV in two patients in China.
Case presentation
Case one
A 24-year-old man was seen in the clinic of a local Hospital on February 8, 2020, for fever with a maximum body temperature of 40 °C, accompanied by fatigue, poor appetite, dizziness. In the past half month, the body weight decreased by 2.5 kg. The patient lived in Wuhan and began having symptoms on February 8. A COVID-19 was diagnosed by SARS-CoV-2 RT-PCR came back positive on February 8 and a chest CT examination, which suggested interstitial lung disease on February 9 (Fig. 1). He was then hospitalized, but his symptoms of fever, chest tightness and shortness of breath were not significantly improved after the symptomatic treatment. On February 18, chest computed tomography revealed ground-glass opacities, which were mainly on the periphery of the lungs (supplementary Fig. 2). Then the patient was transferred to our hospital on February 20 (Table 1). He reported no underlying medical conditions. There was neither blood transfusion nor intravenous drug abuse (sharing of non-sterilized needles). However, it was likely that the patient was a man who has sex with men (MSM).
Routine blood tests revealed a leukocyte count of 6.3 × 109 cells/L (reference range 3.5–9.5 × 109 cells/L) and lymphocyte count of 1.08 × 109 cells/L (reference range 1.1–3.2 × 109 cells/L), lymphocyte percentage 17.0% (reference range 20–50%), C-reactive protein 39.71 mg/L (reference range 0–4 mg/L), hypersensitive C-reactive protein > 10.00 mg/L (reference range 0–4 mg/L). Biochemical test: albumin 38.2 g/L (reference range 40–55 g/L).
The main clinical manifestations were intermittent low fever, night sweat and sore throat. Physical examination showed that the pharynx was congested and swollen, and the tonsil was swollen at grade II. After admission, the patient was given antiviral therapy with Arbidol.
On day 4 of hospitalization, chest computed tomography revealed increased ground-glass opacities (Supplementary file 1). There is no improvement compared with previous CT examination. The patient received moxifloxacin 400 mg once daily for 7 days then he felt relief of sore throat but continuous night sweat and intermittent low fever. SARS-CoV-2 RT-PCR was performed on his throat swabs on day 10, which confirmed a negative result.
On day 12, chest computed tomography revealed ground-glass opacities which were slightly larger than previous one (supplementary Fig. 3). At the night of day 13, the patient’s temperature rose to 40 °C, and then fell down after symptomatic treatment.
On day 13, interleukin 6 was 30.54 pg/mL (reference range < 7 pg/mL), then the patient was treated with Tocilizumab on day 14, together with immunoglobulin and thymosin. After that, there was no fever and night sweat present, but symptom of pharyngeal pain, chest tightness and shortness of breath increased. Physical examination was still found that the tonsil was swollen in degree II and the tonsil was ulcerated.
On day 15, serum SARS-CoV-2 antibody indicated IgM 30.12 (reference range < 10) and IgG 63.52 (reference range < 10). Chest computed tomography on day 20 revealed the texture of both lungs increased, and ground-glass opacities increased in both lungs (supplementary Fig. 4). On day 20, interleukin 6 examination was 688.40 pg/mL. The range of pulmonary lesions increased comparing with CT on day 12.
SARS-CoV-2 RT-PCR assay for detection of coronavirus RNA were performed on his throat swabs on day 21 and day 22 with negative results.
We calculated the percentage change trend of lymphocytes and monocytes and found that after a short period of transient increase, the percentage of lymphocytes showed a gradual and slow downward trend; the percentage of monocytes first increased slowly, and then also showed a slow downward trend (supplementary Fig. 5). The decreasing trend of albumin seemed plain (supplementary Fig. 6).
On day 23, an antigen/antibody combination test on blood gave a HIV-positive result and a Treponema pallidum positive result. The patient’s chest tightness and shortness of breath worsen on day 25 with a progressed CT lesion of both lungs, the density of some lesions became solid (supplementary Fig. 7). We compared the infection percentage of the three CT examinations in hospital by calculating the infection volume through the artificial intelligence technology of chest CT, and we found that the lung infection volume of the patients increased in an equal proportion (supplementary Fig. 8).
On day 25, interleukin 6 examination was 521.00 pg/mL, serum SARS-CoV-2 antibody indicated a reversal. A T cell subsets analysis indicated that the CD4+ T cell count is 13 cells/μL (reference range 500–1600 cells/μL). According to the inter department consultation, the patient’s pulmonary infection was not exclusive of Pneumocystis jirovecii Pneumonia, tuberculosis and cytomegalovirus infection, and then the patient was transfer to a designated hospital for further treatment on day 29.
Case two
A 37-year-old man was referred to our hospital on February 11, 2020 due to fever for more than 1 month (Table 2). At the beginning of January 2020, the patient had fever, the maximum temperature is 39.5 °C, during which chest pain occurred intermittently. In February, chest CT from a local hospital showed multiple exudation in both lungs (Figure lost), and RT-PCR assay for the detection of SARS-CoV-2 was performed on a nasopharyngeal swab and returned negative. The main symptoms of the patient after admission were obvious wheezing after activity which can gradually improve after rest. After admission, the patient was given antiviral therapy with Arbidol.Table 2 Events and timeline of the disease course in patient two in co-infection of HIV and SARS-CoV-2Full size table
Routine blood tests revealed a leukocyte count of 4.2 × 109 cells/L (reference range 3.5–9.5 × 109 cells/L) and lymphocyte count of 1.55 × 109 cells/L (reference range 1.1–3.2 × 109 cells/L), lymphocyte percentage 36.8% (reference range 20–50%), C-reactive protein 96.51 mg/L (reference range 0–4 mg/L), hypersensitive C-reactive protein > 10.00 mg/L (reference range 0–4 mg/L). Biochemical test: albumin 33.2 g/L (reference range 40–55 g/L).
On day 4, the patient had fever at night. Tmax was 39.4 °C, and there was still obvious panting. When panting, the heart rate was fast, accompanied by palpitation. The patient also received moxifloxacin 400 mg once daily for 5 days, methilprednisolone 0.8 mg/kg once daily for 5 days through intravenous route.
On day 10, SARS-CoV-2 RT-PCR was performed on his throat swabs, which confirmed a negative result and chest computed tomography revealed there are multiple large, slightly high-density shadows in both lungs, mostly with ground glass like changes, mainly distributed in the middle and outer zones (supplementary Fig. 9). The patient showed a marked clinical and radiological improvement. His oxygen saturation measured by pulse maintained above 95% on supplemental oxygen via nasal cannula at 15 l per minute in resting state, but decreased rapidly after a little activity, the lowest was about 80%. The patient still felt chest pain, but no D-dimer elevation was found, and the bedside ECG examination also failed to indicate special changes. The cause of chest pain considered the possible involvement of pleura.
On day 11, routine blood tests revealed a leukocyte count of 4.6 × 109 cells/L (reference range 3.5–9.5 × 109 cells/L) and lymphocyte count of 0.91 × 109 cells/L (reference range 1.1–3.2 × 109 cells/L), lymphocyte percentage 19.8% (reference range 20–50%), C-reactive protein 26.06 mg/L (reference range 0–4 mg/L), hypersensitive C-reactive protein > 10.00 mg/L (reference range 0–4 mg/L). Biochemical test: albumin 28.7 g/L (reference range 40–55 g/L).
On day 15, routine blood tests revealed a leukocyte count of 3.8 × 109 cells/L (reference range 3.5–9.5 × 109 cells/L) and lymphocyte count of 0.84 × 109 cells/L (reference range 1.1–3.2 × 109 cells/L), lymphocyte percentage 22.1% (reference range 20–50%), C-reactive protein 11.14 mg/L (reference range 0–4 mg/L), hypersensitive C-reactive protein > 10.00 mg/L (reference range 0–4 mg/L). Biochemical test: albumin 27.5 g/L (reference range 40–55 g/L).
On day 19, chest computed tomography revealed the bilateral lung texture increased, the density of patchy and flocculent increased in large area, and some of them were ground glass like, which was better than that on day 10 (supplementary Fig. 10–11).
On day 21, routine blood tests revealed a leukocyte count of 3.3 × 109 cells/L (reference range 3.5–9.5 × 109 cells/L) and lymphocyte count of 0.56 × 109 cells/L (reference range 1.1–3.2 × 109 cells/L), lymphocyte percentage 17% (reference range 20–50%, supplementary Fig. 12), C-reactive protein 11.65 mg/L (reference range 0–4 mg/L, supplementary Fig. 13), hypersensitive C-reactive protein > 10.00 mg/L (reference range 0–4 mg/L). Biochemical test: albumin 26 g/L (reference range 40–55 g/L, supplementary Fig. 13).
Two times of SARS-CoV-2 RT-PCR assay for detection of coronavirus RNA were performed on his throat swabs on day 19 and day 22, which both confirmed negative results.
On day 22, the patient still has shortness of breath after obvious activity, and sputum is not easy to cough up. After the treatment of antiviral, the patient’s condition did not improve significantly, and there was no absorption of the disease in imaging, so it is possible to combine the infection of Gram-negative bacteria. However, due to the limited conditions, the etiological examination could not be improved, so cefoperazone sulbactam sodium was empirically given and acetylcysteine was given for expectorant treatment.
On day 24, the patient was treated with Tocilizumab together with administration of immunoglobulin and thymosin in that the effect of the previous treatment was not significantly improved and an assay for interleukin 6 was 9.87 pg/mL (day 22). After that, the patient still had intermittent fever, Tmax 37.5 °C. Under the resting state, the blood oxygen saturation was over 95% when given mask oxygen for 5 L/min, but the patient still felt obvious panting after activity.
On day 25, serum SARS-CoV-2 antibody indicated IgM 0.79 (reference range < 10) and IgG 0.63 (reference range < 10). On day 26, interleukin 6 examination was 141.40 pg/mL and an antigen/antibody combination test on blood gave a HIV-positive result and a Treponema pallidum positive result.
On day 27, the patient was asked to receive the antiretroviral treatment in a designated hospital, in light of local epidemic prevention law, until then a COVID-19 was confirmed by a positive SARS-CoV-2 IgM report and the T cell subsets analysis of the patient indicated that the CD4+ T cell count is 23 cells/μL.