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COVID & HIV+ China Report Preliminary Data, How do PLWH Fare?
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IAS COVID WEBINAR:
https://www.iasociety.org/HIV-Programmes/Cross-cutting-issues/COVID-19-and-HIV-Webinars
Co‐infection of SARS‐CoV‐2 and HIV in a patient in Wuhan city, China
11 March 2020
On 28 January 2020, a 61‐years‐old male from Hankou district of Wuhan reported recurrent fever and dry cough for 2 days went to a local fever clinic, which was setup for screening the SARS‐CoV‐2‐infected and suspected subjects. The patient was a heavy smoker of between 20 to 30 cigarettes a day. He had also been diagnosed with type II diabetes 2 year ago and received alogliptin co‐administered with metformin.........Oral therapy with an anti‐HIV drug, lopinavir/ritonavir 400/100 mg per dose twice daily for 12 days, as was advised by Chinese health authority for the treatment of SARS‐CoV‐2 infection, was started on admission.5 The patient also received moxifloxacin 400 mg once daily for 7 days, γ‐globulin 400 mg/kg once daily for 3 days, and methilprednisolone 0.8 mg/kg once daily for 3 days through intravenous route. On 9 February, the patient showed a marked clinical and radiological improvement (Figure 1C).
His oxygen saturation measured by pulse maintained above 95% on supplemental oxygen via nasal cannula at 2 liters per minute. Two additional throat swabs were obtained on 15 February and both were tested negative for SARS‐CoV‐2 RT‐PCR assay. The patient was in stable condition and discharged on 17 February. He was asked to keep isolated at home for two more weeks.
https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25732
-----------------------
In this situation, at high risk of SARS-COV-2 infection in Wuhan City,
individuals with HIV naturally served as an immune suppress model for us to
recognize how the immune system work in duration of SARS-COV-2 infection.
While in 178 HIV/AIDS who took LPV/r (119 cases) or DTG
(59 cases) based ART regimen, no one occurred COVID-19. Although Lpv/r based
ART regimen failed to achieve statistical significance to predict decteasing
occurrence of COVID-19 by the logistic regression analysis, the finding that no
COVID-19 was reported in immunodeficient population who took LPV/r still hold a
great promise.
We also suggest here some anti-HIV drugs, such as LPV/r, had the
potential to be used as PrEP or treatment at early stages of the COVID-19.
We next analyzed laboratory features of these 8 apparent COVID-19 HIV/AIDS
patients. Six of them had CD4 counts>350/μl, and 2 with CD4 counts between
101-350/μl. Intriguingly, in 41 AIDS patients who had low CD4 counts under 100/μl,
no one had reported any typical COVID-19 symptoms.
A Survey for COVID-19 Among HIV/AIDS Patients in Two Districts of Wuhan, China
19 Pages Posted: 13 Mar 2020
https://papers.ssrn.com/sol3/papers.cfm?abstract_id=3550029
Abstract
Background: There were over 49 thousand Coronavirus infected diseases-19(COVID-19) patients in Wuhan city, Hubei province, China, the center of epidemic of the disease. Over 5000 HIV/AIDS patients live in Wuhan. No data on the morbidity of COVID-19 in HIV/AIDS patients have been published to date.
Methods: In this study, we investigated 1178 HIV/AIDS patients in two central districts in Wuhan city. Whether they have any clinical presentations and whether they contacted any confirmed COVID-19 patients were inquired. The results for nucleic acid test (NAT) of SARS-CoV-2 and CT scan in those with clinical symptoms or contact history were investigated. The antiretroviral regimens of all these patients and other information, like age, sex, CD4+T cell counts (CD4 counts), HIV viral load (HIV-VL) were also collected. The risk factors for the COVID-19 in HIV/AIDS patients were analyzed.
Findings: We found 12 individuals in 1174 HIV/AIDS patients who presented clinical symptoms, and 8 of them were confirmed COVID-19. Six of them were NAT confirmed SARS-CoV-2 infection, and 2 were clinical confirmed cases. Six of the 8 COVID-19 patients had CD4 counts> 350/μl, and 2 with CD4 counts between 101-350/μl. All of the 8 patients have a low HIV-VL＜20 copies/ml. The older age is the risk factor to occur COVID-19 in HIV/AIDS. All the 8 COVID-19 patients were from 947 individuals (0.84%) who took NRTI+NNRTI as antiretroviral regimen. In those who have no symptoms, there were another 9 HIV/AIDS patients had close contact with confirmed COVID-19 patients, and only 1 of them was confirmed positive by NAT.
Interpretation: Our findings indicated that the compromised immunity might be the reason that HIV/AIDS patients did not occur inflammatory changes and clinical symptoms, which support the early usage of corticosteroids in treatment for COVID-19. At the same time, the usage of LPV/r may potentially help to prevent or treat COVID-19.
Funding Statement: This work was supported by the grant of the National Natural Science Foundation of China (81471940) to Y.F.
Introduction
As of 2nd March 2020, a total of more than 80,000 of the Coronavirus infected
disease-2019 (COVID-19) patients have been reported in China. More than 49, 300
were in Wuhan, Hubei Province, which is the original epidemic region, and 2227
Wuhan citizens died of this disease1. The virus was transmitted from human to human
at an astonishing speed. By 25th Jan, the basic reproductive number R0 was estimated
to be 2.2-2.68, and the estimated infected number in Wuhan is as huge as 75,000 by a
statistical model 2-4. Although the current reported total number of COVID-19 patients
in Wuhan is less than this estimated one due to the effective measures Chinese
government has taken, there are still hundreds of newly occurred cases come out each
day in Wuhan. One of the reasons for the higher infectiousness of COVID-19 than
severe acute respiratory syndrome (SARS) is that the apparent clinical presentations
of COVID-19 is much more variable than SARS and there are even the asymptomatic
SARS-CoV-2 infectors, no mention the positive rate of nucleic acid test (NAT) is
only 50%, which increase the difficulty for the diagnosis and the corresponding
solutions5.
Several studies have summarized the clinical characteristics of COVID-196-8,
some have reported that the chronic basic diseases, like hypertension, atherosclerosis,
and diabetes, etc, the patients have had previously may relevant with the severity of
the disease7-10. But up till now, none study has been conducted to evaluate the
morbidity and severity of COVID-19 in HIV/AIDS, in which patients are with a
compromised immunity and also in a chronic disease state. Actually, HIV/AIDS
patients were presumed to be at the higher risk of getting infected by the novel virus,
for their susceptibility to even opportunistic pathogens.
At present, there is no vaccine or effective antiviral treatment for COVID-19, to
identify a useful medication as soon as possible is critical for controlling the
increasing huge number of severe cases (more than 14 thousand in whole China and
10 thousand in Wuhan). Remdesivir, Lopinavir/Ritonavir (LPV/r), Ribavirin, Arbidor,
and Chloroquine, etc, have already been tried in COVID-19 treatment, and
Remdesivir is now under a registered clinical experiment. The combination protease
inhibitor, LPV/r, was proved to target both HIV and coronaviruses11, and the national
guidelines for diagnosis and treatment of COVID-19 (from the 1st-6th) also suggested
to treat patients with LPV/r. The exact effect of LPV/r in treating the SARS-CoV-2
caused disease still need more observation. But since HIV/AIDS patients might take
LPV/r as a routine of the antiretrovirus therapy (ART), it provides us a natural study
object to observe whether LPV/r can be used as a pre-exposure prophylaxis (PrEP) for
SARS-CoV-2, like the PrEP for HIV, people who do not infected with HIV but at
high risks can take antiretroviral drug every day to prevent the infection.
Therefore, in this study, we investigated 1178 HIV/AIDS patients in Wuhan and
surveyed their health status and whether they were directly contacted with confirmed
COVID-19 patients. The percentage of COVID-19 patients with clinical symptoms in
this cohort was calculated. The association between the occurrence of COVID-19 and
the patient's ART, HIV viral load (HIV-VL), and CD4+T cell counts (CD4 counts)
were analyzed. By this investigation, we hope to find out the risk factors of
COVID-19 in HIV/AIDS population, and evaluate the role of ART in preventing or
treating COVID-19.
Results
1. There were 8 COVID-19 out of 1174 investigated HIV/AIDS patients.
Our investigators surveyed 1174 HIV+ individuals who were recorded in the the
AIDS Comprehensive Prevention and Control Data Information Management System
of Chinese Center for Disease Control and Prevention. We found 12 HIV/AIDS
individuals who presented clinical symptoms, and 8 of them were confirmed
COVID-19. Moreover, 6 of them were laboratory confirmed SARS-CoV-2 infection
by both CT scan and NAT, and 2 were clinical confirmed cases by CT scan only
(NATs were negative). Among these 8 patients, 7 were males (88%) and 1 was female
(13%). Similarly, in 1166 other HIV/AIDS patients who didn't report any typical
symptoms of COVID-19, 1045 were males (90%) and 121 were females (10%). The
rate of COVID-19 in people with HIV/AIDS was about 0.68% (95%CI: 0.29% -
1.34%), a little higher than the morbidity of population in Wuhan (∼0.5%, as 49
thousand out of 9 million according to the report by the end of February 27, 2020),
while less than the estimated morbidity as 0.83% (75 thousand out of 9 million)4. Till
March 3, 2020, 6 of the COVID-19/HIV patients were mild cases, 1 was severe cases,
and 1 was critical case who died.
According to our survey, among those without any symptoms, another 9
HIV/AIDS patients reported close contact with confirmed or suspected COVID-19
patients. Only 1 of them was NAT positive (inapparent infector), who was with a CD4
counts as 27/μl. This individual occurred Kaposi's sarcoma, and was under chemo
therapy. The ART of this patient had started just one month before accepting the
investigation. The investigation scheme is summarized in Fig.2.
2. Comparison of characteristics between HIV/AIDS individuals with COVID-19 or
not
As shown in Table 1, we compared the characteristics between HIV/AIDS
individuals with COVID-19 or not. The median age of these COVID-19 patients (n=8)
was 57.0 years old (47.5-61.5), which was significantly (P=0.010) older than the age
(36.0, 30.0-51.0) of those without COVID-19 (n=1166). This finding was consistent
with that the elder males had a higher infection rate of SARS-CoV-2 in HIV negative
population. 9,10,14
We next analyzed laboratory features of these 8 apparent COVID-19 HIV/AIDS
patients. Six of them had CD4 counts>350/μl, and 2 with CD4 counts between
101-350/μl. Intriguingly, in 41 AIDS patients who had low CD4 counts under 100/μl,
no one had reported any typical COVID-19 symptoms.
When we analyzed the HIV-VL of these 8 COVID-19/HIV patients, we found all
of them have a low HIV-VL as less than 20 copies/ml. There were no positive
symptoms were reported in 295 AIDS patients who had virus loads more than 20
copies/ml.
It's worth noting that all 8 COVID-19 patients' ARV regimens are Nucleoside
Reverse Transcriptase Inhibitors (NRTIs) and Non-Nucleoside Reverse Transcriptase
Inhibitors (NNRTIs). While in the patients who haven't started ART, or who were
taking protease inhibitor (PI), like LPV/r, Elvitegravir/cobi (EVG/c), or who were
taking integrase inhibitors, like Dolutegravir (DTG), Raltegravir (RAL), and
Bictegravir (BIC), there were no COVID-19 being reported. But there was no
significant difference for the morbidity of COVID-19 between the patients taking
each ART regimen. While 28 individuals who did not start ART were temporarily
"waived" by COVID-19.
3. Analysis of risk factors for the occurrence of COVID-19
We then analyzed the relevance of some risk factors for the occurrence of
COVID-19 using Logistic regression. We found that only the age of the patients
showed significant relevance with the occurrence of COVID-19 (P<0.05), ie, like we
observed above, the older patients might have more chance to occur COVID-19.
Other factors, no matter the gender or the CD4 counts, or the HIV-VL, or the ART
regimen didn't show any relevance with the occurrence of COVID-19.
Discussion
The epidemic of COVID-19 has been outbreaking in Wuhan, Hubei Province,
and soon spreading to whole China since January 20206,15. Although after taking the
emergent strategies, the number of newly occurred COVID-19 in China is decline, the
total infected number in Wuhan city and Hubei province is still extraordinarily huge.
Moreover, there are more sparks of newly occurred cases in Korea, Iran, Japan, and
Singapore, etc, which indicate a probability of a global pandemic.
Although it is now broadly accepted that SARS-COV-2, as an airborne pathogen,
majorly cause pulmonary infection and further lesion, because 1) most of the patients
presented with significant respiratory symptoms; 2) by analyzing the structure of
SARS-COV-2, the characteristic SPIKE protein on the virus can bind to the
angiotensin-converting enzyme 2 (ACE2)16, which broadly expressed on the epithelial
cells of the lung. While since more and more patients were investigated, symptoms
indicated multiple organ injuries were found, like palpitation, which indicated heart
involvement, and diarrhea, which indicated abnormal intestine function17. Whether
these organs lesion were attacked by the virus directly or by other mechanisms is
unclear. Actually, according to the clinical characteristics, many cases presented
extremely abnormal white blood cell numbers and lymphocyte counts, which
indicated that inflammatory responses caused by the virus may be violent. The
pathological findings also showed there were a lot of inflammatory cells being found
infiltration in the lungs, the heart and liver of the COVID-19 patients18,19. The
pathogenesis of COVID-19 is still unclear, but it seems that so called "inflammatory
storm" may play a role in SARS-COV-2 caused multi-organ injury.
In this situation, at high risk of SARS-COV-2 infection in Wuhan City,
individuals with HIV naturally served as an immune suppress model for us to
recognize how the immune system work in duration of SARS-COV-2 infection. In
our study, HIV/AIDS population exhibits a relatively "normal" positive rate on
occurring COVID-19 but not a higher rate, unexpectedly. We observed the 8
COVID-19 patients from 1174 HIV+ individuals. Of note, all of these 8
COVID-19/HIV patients had a feature of low HIV-VL (<20 copies/ml) but relatively
higher or normal CD4 counts than other patients. This finding strongly suggested that
a relatively normal immune system probably facilitates the dominant infection, or
more accurately, causes the pathological changes to give rise to the symptoms.
On the other hand, our finding also indicated that a compromised immune
system with a lower CD4 counts level might waive clinical symptoms. Considering
there were a lot of asymptomatic SARS-COV-2 infected individuals being reported,
although we don't have effective strategies to screening all of the HIV/AIDS patients,
we may speculate that some of them may be actually infected but present with no
symptoms. This finding probably supports the hypothesis that a lower active immune
status might protect the human body from a severe viral attack other than the immune
storm, such as SARS and middle east respiratory syndrome (MERS). In this context,
although experts objected the usage of corticosteroids in treatment with COVID-1920,
the Chinese national recommendations for diagnosis and treatment of COVID-19
(from the 1st-6th) prefer this anti-inflammatory treatment in short time for the
patients with rapid progress for preventing severe multi-organ injury .
Given the scale and rapid spread of the SARS-CoV-2, there is an immediate need
for medicines that help to deal with the disease before effective vaccine being
available. Some medicines (Atazanavir, LPV/r, DTG, etc) were recommended by
researchers performing drug screening models21,22. Meanwhile, some potential
effective medicines (LPV/r, Remdesivir, Darunavir, etc) were used in clinic or clinical
trial to treat COVID-19. Especially for LPV/r, a protease inhibitor, is recommended
by national recommendations for diagnosis and treatment of COVID-19 (from the
1st-6th) based on its history of treating SARS and MERS 23,24. To be noticeable, in this
study, we reported firstly that the 8 COVID-19 patients were from 947 individuals
(0.84%) who took NRTI+NNRTI as ART regimen. This rate is higher than morbidity
of population in Wuhan (∼0.5%, as 47 thousand out of 9 million according to the
report by the end of February 27, 2020), while similar with the estimated morbidity as
0.83%, as 75 thousand out of 9 million4.This result indicates that NRTI+NNRTI could
not prevent or treat COVID-19, which keeps consistent with the main results of drug
screening experiments. While in 178 HIV/AIDS who took LPV/r (119 cases) or DTG
(59 cases) based ART regimen, no one occurred COVID-19. Although Lpv/r based
ART regimen failed to achieve statistical significance to predict decteasing
occurrence of COVID-19 by the logistic regression analysis, the finding that no
COVID-19 was reported in immunodeficient population who took LPV/r still hold a
great promise. We also suggest here some anti-HIV drugs, such as LPV/r, had the
potential to be used as PrEP or treatment at early stages of the COVID-19.
In the present study, we found that in HIV/AIDS population, all of those
combined COVID-19 patients had a relatively normal CD4 counts, which indicated a
relatively normal immune function. None of those COVID-19/HIV patients took
LPV/r based ART regimen, which seemed to support the use of LPV/r in PrEP and
cope with COVID-19. To summarize, 1) we recommend to try LPV/r for PrEP of
COVID-19 in those with high risk factors, like medical workers or volunteers who
cope with COVID-19; 2) The usage of LPV/r should be at the early phase of the
disease, for in later phase, the organ injury may cause by inflammation but not virus;
3) For the probable inflammation, anti-inflammatory treatment, like corticosteroids,
may be taken into account. Our investigation based on only two districts of Wuhan,
and less than two thousand individuals were enrolled, large scale investigation is still
in need to illustrate this question more clearly.
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