COVID-19 incidence in this study was 0.083 (95% CI 0.074–0.092), which is higher than a study in Madrid [(0.067 (95% CI 0.057–0.079) . The pooled incidence proportion in 7 other studies was 0.009 (95% CI 0.006–0.011), but this meta-analysis only represented studies in 2020 . Most of the COVID-19 cases observed in this study had no symptoms or mild symptoms (86.3%). Rial-Crestelo et al. also observed a high proportion of patients with asymptomatic or mild disease in Spain (75.3% of 158 patients) , while a study in China showed 60% of 2464 PLHIV with COVID-19 infection being asymptomatic . The proportion of severe and critical cases was smaller in our study (6.7%), which showed different patterns, although with limited numbers of COVID-19 cases in PLHIV. Mirzaei et al., which summarized 212 available data from 25 case reports and small studies, described the proportion of severe-critical case as 33.5% of all PLHIV with COVID-19 infection .
This study observed a lower mortality rate (3.2%) compared to previous reports. Ssentongo et al. showed pooled mortality rate for studies in 2020 was 12.65% (95% CI 6.81–22.31%) , while Liang et al. calculated a pooled mortality rate of 14 studies up to March 2021 was 8.814% . We believe that more participants and longer observation time can better describe the proportion. However, these findings must be interpreted cautiously since a recent meta-analysis still found that PLHIV have a higher risk of death compared to non-HIV COVID-19 patients (HR = 1.76, 95% CI 1.31–2.35) .
Moreover, COVID-19 vaccination in PLHIV might change morbidity and mortality rates in the future. This study reported COVID-19 cases from March 2020 to December 2021 while the Indonesian government just started COVID-19 vaccination program to general population in June 2021. Therefore, we believe that not many COVID-19 patients in this study had been vaccinated though the data was not available.
The hospitalization rate of PLHIV with COVID-19 infection was found to be 14%, which is still within the range of other studies (13.8–58%) [9, 11, 14, 15, 18]. This low proportion of hospitalization does not necessarily mean that the number of patients who needed hospitalization was low. As shown in Fig. 1 [19, 20], more than half of the COVID-19 cases occurred during the second wave of the pandemic (June to August 2021) when the delta variant spread, although genomic sequencing was not routinely performed. Some patients may have had difficulties finding hospital care due to the limited capacities of health facilities during the increasing demand for hospitals experienced during waves .
Fifteen patients (4.4%) were unaware of their HIV diagnosis before contracting COVID-19. In the newly-diagnosed HIV patients, there were several reports of co-infection of COVID-19 and Pneumocystic jirovecii pneumonia [22, 23]. Some opportunistic pulmonary infections have similar clinical and radiological symptoms to COVID-19, including cytomegalovirus and Pneumocystic jirovecii pneumonia. Thus, other causes of respiratory infection than SARS-CoV-2 must still be considered even during this massive pandemic.
This study identified several factors related to developing severe COVID-19 infection in PLHIV. As in the general population, the severity of COVID-19 infection was found to be associated with either diabetes, hypertension, obesity, chronic kidney disease or cardiovascular disease [1, 11, 17]. This finding contributes to the understanding that comorbidities strongly correlate with severe COVID-19 outcomes [24,25,26,27].
Persistent immune dysfunction may be important in severe COVID-19 infection. This study indicated that a low CD4 count (less than 200 cells/mm3) was associated with COVID-19 severity. This finding was in accordance with other studies. Hoffman et al. showed that a current CD4 count of less than 250 cells/mm3 significantly correlates with the risk of severe COVID-19 . In addition, Nomah et al. found that a low CD4 count (less than 200 cells/ mm3) was associated with worse outcomes from HIV-COVID-19 co-infection . Jassat et al. showed that PLHIV with a history of CD4 count of less than 200 cells/mm3 were twice as likely to die in hospital than those with a CD4 count of 200 cells/mm3 This may be due to the well-described lymphopenia that occurs in severe COVID-19 . Zhang et al. evaluated studies reporting CD4 and CD8 count in severe COVID-19 patients, but not specifically PLHIV, indicating that both CD4 and CD8 T cell counts were significantly lower in the severe group compared to the non-severe group . Therefore, both T cell counts may be considered as biomarkers for predicting severe COVID-19. Not using ART was also found to be a significant predicting factor of COVID-19 severity. HIV infection without ART can be a dangerous comorbidity of COVID-19 infection. Jassat et al. found that PLHIV who were not on ART were more likely to die in hospital than PLHIV who were on ART (aOR = 1.45, 95% CI 1.22–1.72) . A study of T cell dynamics during COVID-19 infection has revealed that COVID-19 leads to a rapid augmentation of the T-cell exhaustion process initially caused by HIV, and this T cell degradation was observed to be the most pronounced in PLHIV not using ART .
To the authors’ knowledge, this is the first report on SARS-CoV-2 among PLHIV in Indonesia, and one of a limited number of studies that include PLHIV with a range of opportunistic infections. PLHIV with opportunistic infections are considered as part of the high-risk population for COVID-19 infection and the worse outcome population. In this study, most of the opportunistic infections diagnosed before or during COVID-19 infection were also severe infections, such as extrapulmonary tuberculosis, toxoplasma encephalitis, cryptococcal meningitis, histoplasmosis, and esophageal candidiasis. These kinds of infections also increase the risk of mortality among PLHIV. These findings also contribute important information about managing concurrent AIDS-defining illness during the COVID-19 pandemic. Though not statistically significant, a previous study in three European countries showed that 40% of its PLHIV population who had severe or critical COVID-19 infection had AIDS-defining illness while only 27% of PLHIV with mild to moderate COVID-19 had AIDS-defining illness . The COVID-19 pandemic has disrupted public health priorities, including the fight against HIV. There have been some reports of late presenters of an AIDS-defining life-threatening condition as a result of difficulties accessing hospital care . In addition, during the COVID-19 pandemic, there have been many reports indicating a reduction in HIV testing rates in many countries [33,34,35].