HIV and Covid-19 coinfection Questions:

###### tags: `groupthink` # HIV and Covid-19 coinfection Questions: ## Definition of chronic COVID (vs long COVID) When looking at articles, a careful interpretation of what is described as `chronic COVID` may be important. It is possible that this is a loosely defined term that not many people distinguish. In fact, to me, it is unclear if they are talking about the symptoms in the presence of the virus or after virus clearance (I guess symptom is really all that matters clinically.) Let's make sure what authors really mean when they say chronic or long COVID. For our particular interest, chronic COVID must have the virus present. Thus, we would want to have information about the following in addition to the information about the co-infection of interest: - the length of illness - the definition of on-going COVID (the cycle threshold, Ct?) --- ### Median Duration of COVID #### Summary - Median **symptom** duration: 11 days - Median **PCR positive viral load** duration: 28 days [Attributes and predictors of long COVID](https://www.nature.com/articles/s41591-021-01292-y?ftag=YHF4eb9d17) > The COVID Symptom Study is **a mobile application** launched in response to the COVID-19 pandemic. ... From these, we selected 4,182 individuals who met the inclusion criteria to investigate the duration of persistent symptoms in COVID-19 (Extended Data Fig. 1). ... For individuals who had ***a positive swab*** for COVID-19 (n = 4,182 from the UK, the US and Sweden), **the overall median symptom duration was 11 (interquartile range (IQR), 6–19) days**, with 558 (13.3%) people who met the LC28 definition (median (IQR), 41 (33–63) days). Of those, 189 (4.5%) met the definition for LC56 (duration ≥ 56 d) and **108 (2.6%) for LC84 (duration ≥ 84 d; all percentages were calculated with respect to the overall sample, n = 4,182)**. In contrast 1,591 (38.0%) individuals had short COVID (median (IQR) symptom duration, 6 (4–8) days). The proportions were comparable in all three countries (UK: 3,491, US: 218, Sweden: 473; LC28: UK 13.3%, US 16.1%, Sweden 12.1%; P = 0.35; LC56: UK 4.7%, US 5.5%, Sweden 2.5%; P = 0.07). > Fig. 1: Distribution of disease duration and age effect on duration. > ![Fig. 1: Distribution of disease duration and age effect on duration.](https://i.imgur.com/J0wNT9M.png) [Post-acute COVID-19 syndrome](https://www.nature.com/articles/s41591-021-01283-z) > For the purpose of this review, we defined post-acute COVID-19 as persistent symptoms and/or delayed or long-term complications of SARS-CoV-2 infection beyond 4 weeks from the onset of symptoms (Fig. 1). > Fig. 1 | Timeline of post-acute COVID-19. > ![Fig. 1 | Timeline of post-acute COVID-19. ](https://i.imgur.com/IabSCtR.png) ### Clinical definition #### Summary - Long COVID will generally indicate symptoms after infection clearance. Thus, it would be important to find data about chronic or persistent SARS-CoV-2. I found a definition for "long COVID" or Post Acute Sequelae of SARS-CoV-2 Infection (PASC), but not many scholarly papers are using the latter term. - I have not yet found a good clinical definition of chronic or persistent SARS-CoV-2. [Long COVID and chronic COVID syndromes](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675759/#jmv26587-bib-0002) > Long COVID or postacute COVID (symptoms beyond 3 weeks) and chronic post‐COVID syndrome (beyond 12 weeks) are multisystem syndromes and need a multifaceted approach to tackle the physical, cognitive, psychological, social, and vocational domains of this health condition. [Defining Post-COVID Symptoms (Post-Acute COVID, Long COVID, Persistent Post-COVID): An Integrative Classification](https://www.mdpi.com/1660-4601/18/5/2621/htm) > Based on the above considerations, we would like to propose the following classification for post-COVID symptoms (pending of validation in future studies). This categorization should be taken as a dynamic and complex process that may integrate potential biological, psychological, and social factors which could predispose or promote the development of post-COVID symptoms. This classification is also conditioned by whether a patient has required hospital admission or not. > - Transition Phase: Symptoms potentially associated with acute COVID-19: symptoms up to 4–5 weeks; > - Phase 1: Acute post-COVID symptoms: symptoms from week 5 to week 12; > - Phase 2: Long post-COVID symptoms: symptoms from week 12 to week 24; > - Phase 3: Persistent post-COVID symptoms: symptoms lasting more than 24 weeks. [NIH white paper: What is the typical recovery from COVID-19?](https://www.ninds.nih.gov/Current-Research/Coronavirus-and-NINDS/nervous-system#recovery) > Fortunately, people who have mild to moderate symptoms typically recover in **a few days or weeks**. However, some people who have had only mild or moderate symptoms of COVID-19 continue to experience dysfunction of body systems—particularly in the lungs but also possibly affecting the liver, kidneys, heart, skin, and brain and nervous system—months after their infection. In rare cases, some individuals may develop new symptoms (called sequelae) that stem from but were not present at the time of initial infection. People who require intensive care for Acute Respiratory Distress Syndrome, regardless of the cause, usually have a long period of recovery. Individuals with long-term effects, whether following mild or more severe COVID-19, have in some cases self-identified as having “long COVID” or “long haul COVID.” **These long-term symptoms are included in the scientific term, Post Acute Sequelae of SARS-CoV-2 Infection (PASC).** ### Clinical interest #### Summary - Clinically, it may be interesting to have emphasis on patients or host (symptoms and physiology). But what is it like in terms of the virus? How does the virus change during persistent COVID? How does SARS-CoV-2 interact with other viruses that may be present? [Persistent Symptoms in Patients After Acute COVID-19 (1520 citations)](https://jamanetwork.com/journals/jama/fullarticle/2768351/) > Figure. COVID-19–Related Symptoms > ![Figure. COVID-19–Related Symptoms](https://i.imgur.com/F33THwq.png) [Attributes and predictors of long COVID](https://www.nature.com/articles/s41591-021-01292-y?ftag=YHF4eb9d17) // repeated reference > Long COVID was characterized by symptoms of fatigue, headache, dyspnea and anosmia and was more likely with increasing age and body mass index and female sex. --- ## 1. All case studies when covid is chronic and there is sequence data.  [SARS-CoV-2 evolution during treatment of chronic infection](https://www.nature.com/articles/s41586-021-03291-y.pdf) - Summary: - Chronic infection with SC2 leads to viral evolution and reduced sensitivity to neuralizing antibodies in an immunosuppressed individual treated with convalescent plasma, by generating whole-genome ultra-deep sequences for the 23 time points that span 101 days and using in vitro techniques to characterize the mutations revealed by sequenceing... These data reveal strong selection on SC-2 during convalescent plasma therapy, which is associated with the emergence of viral variants that show evidence of reduced susceptibility to neutralizing antibodies in immunosuppressed individuals. - Length of Having COVID: - 101 days - On-going COVID definition: - Ct ≤ 36 - COVID Data: - Number of Patient(s): 1 - Time points: 23 - Long-read sequencing data that support the findings of this study have been deposited in the NCBI SRA database with accession codes **SAMN16976824~SAMN16976846 under BioProject PRJNA682013**. - Short reads and data used to construct figures were deposited at https://github.com/Steven-Kemp/sequence_files [Case Study: Prolonged Infectious SARS-CoV-2 Shedding from an Asymptomatic Immunocompromised Individual with Cancer](https://reader.elsevier.com/reader/sd/pii/S0092867420314562?token=ACDECBA5F2B1A28A8BB81F14B94BFD0B568EFA8D38F271B47C30E83A30C63D756852CBF947CB49CDE5F7D2CD27F8D443&originRegion=us-east-1&originCreation=20211012115047) - Summary - Immunocompromised indiviual with chronic lymphocytic leukemia and aquired hypogammaglobulinemia who became persistently infected with SARS-CoV-2 - Although asymptomaticthroughout the course of infection, shedemonstrated prolonged shedding ofinfectious SARS-CoV-2 virus and RNA - Showing that even though asymptomatic, can still spread virus relatively easily - Length of Having COVID: - 105 days - 105 days for the detection of the virus, 70 days for virus shredding - On-going COVID definition: - NA - COVID Data: - Number of Patient(s): 1 - Time points: 4 - The data and the supplementary tables from this study have been deposited to Mendeley Data. - 4 Genbank patient samples d49, d70, d85, and d105 (MT982403;MT982402;MT982405;MT982406) - 2 Genbank SARS-CoV isolates of samples d49 and d70 (MT982401;MT982404) - https://dx.doi.org/10.17632/3n377gv8kb [Chronic SARS-CoV-2 infection and viral evolution in a hypogammaglobulinaemic individual.](https://www.medrxiv.org/content/10.1101/2021.05.31.21257591v1.full.pdf) - Summary: - After five months of persistent SARS-CoV-2 replication in this immunocompromised patient, the virus was found to have evolved rapidly between the day 58 and 158 samples. Specifically, it acquired six additional non-synonymous SNPs and a deletion which then became fixed in the viral genome over the duration of infection. There were three specific mutations in the spike protein for which there is evidence of biological effect. The ΔH69/ΔV70 deletion is present in the B.1.1.7 VOC (26). The mutation came to attention as one of a cluster of five mutations in the spike protein associated with spill over of SARS-CoV-2 to mink. Of the five mutations, a combination of ΔH69/ΔV70 and Y453F are sufficient to evade neutralising antibody recognition (29). The same combination was identified in the viral sequence present in a persistently infected immunocompromised patient (30), suggesting convergent evolution - Length of Having COVID: - ~306 days - > 290 days, longest known in literature. - On-going COVID definition: - NA - COVID Data: - Number of Patient(s): 1 - Time points: 7 - Check out Table 1: SARS-CoV-2 genome detection in swab samples. - 7 in ENA (ERR4422451;ERR4616078;ERR4780220;ERR5510862;ERR5405452;ERR5502292;ERR5498086) - 2 in GISAID (EPI_ISL_469397;EPI_ISL_1103757) [Persistence and Evolution of SARS-CoV-2 in an Immunocompromised Host](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673303/) - Summary: > A 45-year-old man with severe antiphospholipid syndrome complicated by diffuse alveolar hemorrhage,1 who was receiving anticoagulation therapy, glucocorticoids, cyclophosphamide, and intermittent rituximab and eculizumab, was admitted to the hospital with fever. - Length of Having COVID: - 152 days - On-going COVID definition: - NA - COVID Data: - Number of Patient(s): NA - Time points: 9 - In Supplementary Appendix - 9 in GISAID (EPI_ISL_593480;EPI_ISL_593557;EPI_ISL_593558;EPI_ISL_593555;EPI_ISL_593478;EPI_ISL_593479;EPI_ISL_593556;EPI_ISL_593553;EPI_ISL_593554)  [Emergence of multiple SARS-CoV-2 mutations in an immunocompromised host](https://www.medrxiv.org/content/10.1101/2021.01.10.20248871v1.full.pdf+html) - Summary: > Here, we describe the detection of high levels of replication-competent SARS-CoV-2 in specimens taken from the respiratory tract of a B-cell depleted patient up to 154 days after initial COVID-19 diagnosis concomitant with the development of high mutation rate. In this patient, a total of 11 nonsynonymous mutations were detected in addition to the Y144 deletion in the spike protein of SARS-CoV-2. - Length of Having COVID: - 134 days - On-going COVID definition: - NA - COVID Data: - Number of Patient(s): 1 - Time points: 2 - d0 and d134, compared with two other patients with no metadata (GISAID EPI_ISL_732533, EPI_ISL_732560): - 2 in GISAID d0 and d134 (EPI_ISL_732538;EPI_ISL_732658) [Within-host evolution of SARS-CoV-2 in an immunosuppressed COVID-19 patient: a source of 1 immune escape variants](https://www.medrxiv.org/content/10.1101/2021.04.30.21256244v1.full.pdf) - Summary: > Here, we studied the long-term SARS-CoV-2 infection in an immunosuppressed organ transplant recipient. Frequent respiratory specimens were tested for variant viral genomes by RT-qPCR, next-generation sequencing (NGS), and virus isolation. - Length of Having COVID: - 140 days - On-going COVID definition: - Ct ≤ 40 - Figure 1 legend - COVID Data: - Number of Patient(s): 1 - Time points: 9 - Extended Data Table 2, also Figure 2 legend - 9 in GISAID d0, d7, d14, d42, d56, d59, d71, d105, and d140 (EPI_ISL_852709;EPI_ISL_852671;EPI_ISL_852667;EPI_ISL_852659;EPI_ISL_852809;EPI_ISL_852808;EPI_ISL_852805;EPI_ISL_852807;EPI_ISL_852806) --- ## 2. Any evidence that Covid disease course is longer in HIV positive subjects.  [COVID-19 Outcomes Among Persons Living With or Without Diagnosed HIV Infection in New York State](https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775827) - Summary: - Person living with HIV (PWH) covid-19 diagnosis more likely to be hospitalized and more likely to die  [Coronavirus disease 2019 (covid-19) infection among people with human immunodeficiency virus in New York City: a population-level analysis of linked surveillance data ](https://pubmed.ncbi.nlm.nih.gov/33252620/) - Summary: > PWH were not overrepresented among COVID-19 cases. However, compared with NYC COVID-19 cases overall, a greater proportion of PWH had adverse COVID-19-related outcomes  [Patterns of HIV and SARS-CoV-2 co-infection in Wuhan, China](https://onlinelibrary.wiley.com/doi/10.1002/jia2.25568) - Summary: > Here we present the clinical and laboratory patterns in 14 co-infected cases, including three asymptomatic SARS-CoV-2 carriers in Wuhan, China, from 16 February to 30 April 2020.  [Co‐infection of SARS‐CoV‐2 and HIV in a patient in Wuhan city, China](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7228399/) - Summary: > Severe cases developed life‐threatening complications, such as respiratory failure, shock, and multiple organs dysfunction. 4 We report on an identified unique severe case involving co‐infection of SARS‐CoV‐2 and HIV.  [COVID-19 in patients with HIV: clinical case series](https://www.thelancet.com/journals/lancet/article/PIIS2352-3018(20)30111-9/fulltext) - Summary: - NA  [SARS-CoV-2 and HIV coinfection: clinical experience from Rhode Island, United States](https://onlinelibrary.wiley.com/doi/10.1002/jia2.25573) - Summary: - NA  --- ## 3. Any studies that sequences HIV and SC2 from the same people.  #### Note: We were able to find some HIV patients with SARS-CoV-2. Some of these patients had SARS-CoV-2 sequence data. HIV sequence data was rare. [Long-Term Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infectiousness Among Three Immunocompromised Patients: From Prolonged Viral Shedding to SARS-CoV-2 Superinfection](https://academic.oup.com/jid/article/223/9/1522/6131370) - Summary: > In this study, we describe 3 deeply immunocompromised patients, each with different clinical evolutions. We observed (1) the patients’ epidemiological, clinical, and serological data, (2) infectiousness using viral culture, and (3) viral mutations accumulated over time. - Length of Having COVID: - 111 days - On-going COVID definition: - NA - COVID Data: - Number of Patient(s): 3 - Time points: 3~4 - Nanopore ONT - GISAID (EPI_ISL_833191~EPI_ISL_833200) - HIV Data: - NA - HIV details: - **Patient 1 has HIV as per Table 1.** - ART-naïve patient; this information as per [Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection](https://www.medrxiv.org/content/medrxiv/early/2021/06/04/2021.06.03.21258228.full.pdf) > Here is one other documented case of prolonged infection in a person with HIV - in that case the person was ART-naïve with profound immunosupp ression and genome sequencing revealed only a single emergent mutation in spike (T719I) at day 53. [Persistent SARS-CoV-2 infection and intra-host evolution in association with advanced HIV infection](https://www.medrxiv.org/content/medrxiv/early/2021/06/04/2021.06.03.21258228.full.pdf) - Summary: > We collected nasopharyngeal swabs and blood specimens on day 6… > We performed SARS-CoV-2 whole genome amplification by multiplex PCR using primers designed on Primal Scheme > We performed HIV-1 sequencing on all specimens with viral load >1000 copies/mL using the Illumina MiSeq instrument - Length of Having COVID: - 216 days - On-going COVID definition: - NA - COVID Data: - Number of Patient(s): 1 - Time points: 7 - whole genome amplification by multiplex PCR using primers designed on Primal Scheme - HIV Data: - MiSeq - Availability: - Not public yet, but a collaborator of the lab - HIV details: - HIV-positive female in late 30s - On ART since 2006   --- ## To review - [x] [Cross-neutralization of SARS-CoV-2 by HIV-1 specific broadly neutralizing antibodies and polyclonal plasma](https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1009958) - [x] [HIV and COVID-19 Virtual Issue](https://onlinelibrary.wiley.com/doi/toc/10.1002/(ISSN)1758-2652.hiv-covid-19-vi) - [ ] [Risk factors for COVID-19-related in-hospital mortality in a high HIV and tuberculosis prevalence setting in South Africa: a cohort study](https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00151-X/fulltext) (Discusses a number of comorbidities, data is through survey) - [ ] [Safety and immunogenicity of the ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 in people living with and without HIV in South Africa: an interim analysis of a randomised, double-blind, placebo-controlled, phase 1B/2A trial](https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00157-0/fulltext) - [ ] [SARS-CoV-2 immunity and HIV infection: total recall?](https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00097-7/fulltext) - [x] [Overview of SARS-CoV-2 infection in adults living with HIV](https://www.thelancet.com/journals/lanhiv/article/PIIS2352-3018(21)00070-9/fulltext) Table 1 has a lot of links about HIV patients with SARS-CoV-2. - [ ] [Epidemiology and outcomes of COVID-19 in HIV-infected individuals: a systematic review and meta-analysis](https://www.nature.com/articles/s41598-021-85359-3) - [ ] [HIV/SARS-CoV-2 coinfection: A global perspective]( https://onlinelibrary.wiley.com/doi/10.1002/jmv.26321) * https://clinicalinfo.hiv.gov/en/guidelines/covid-19-and-persons-hiv-interim-guidance/interim-guidance-covid-19-and-persons-hiv ( See References section) * ~~https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2775827~~ * https://www.sciencedirect.com/science/article/pii/S1201971220322530 * https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7536551/ * https://wwwnc.cdc.gov/eid/article/27/10/21-1461_article * https://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-020-05480-y * https://www.frontiersin.org/articles/10.3389/fmed.2020.00216/full * https://www.dovepress.com/sars-cov-2-and-human-immunodeficiency-virus-pathogen-pincer-attack-peer-reviewed-fulltext-article-HIV * Clinical Features and Outcomes of Patients With Human Immunodeficiency Virus With COVID-19 https://pubmed.ncbi.nlm.nih.gov/32407467/ * SARS-COV2 infection in 30 HIV-infected patients followed-up in a French University Hospital https://www.ijidonline.com/article/S1201-9712(20)32152-4/fulltext * https://academic.oup.com/cid/advance-article/doi/10.1093/cid/ciab758/6362722 * Prolonged Severe Acute Respiratory Syndrome Coronavirus 2 Replication in an Immunocompromised Patient https://academic.oup.com/jid/article/223/1/23/5934826 9 time-point samples from 1 patient but does not share data - [x] Prolonged SARS-CoV-2 shedding and mild course of COVID-19 in a patient after recent heart transplantation https://onlinelibrary.wiley.com/doi/epdf/10.1111/ajt.16133 Has 1 patient that the authors are looking at, but no data shared. Instead Table 1 has a bunch of references that I can look at. - [x] A Possible Role of Remdesivir and Plasma Therapy in the Selective Sweep and Emergence of New SARS-CoV-2 Variants https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8348317/ Has 1 patient, no data, but Table 1 references. * The longest persistence of viable SARS-CoV-2 with recurrence of viremia and relapsing symptomatic COVID-19 in an immunocompromised patient – a case study https://academic.oup.com/ofid/advance-article/doi/10.1093/ofid/ofab217/6257145 Has 1 patient, no data

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