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By Jamshed Arslan, Pharm D, PhD
Post-acute infection syndrome (PAIS) is a phenomenon where ill effects of an infection persist even after the infection itself is over. PAIS in the case of COVID is called the long COVID or post-COVID conditions (PCC): sequelae of SARS-CoV-2 infection that persist for months/years after the initial infection and/or symptoms. People facing PCC are often called the COVID long-haulers. It must be noted that no consensus on the definition of long COVID exists because of the heterogeneity of patients and their symptoms.
Long COVID was formally recognized about six months after the start of the 2019 pandemic as the emergence or persistence of neurological and/or respiratory symptoms of SARS-CoV-2 infection that do not vanish when the infection is over. The most common neurological symptom is prolonged fatigue. Respiratory symptoms usually include a cough and breathlessness. More diverse symptoms like muscle ache are also not uncommon. The reality is that the symptoms can affect any part of the body and may even trigger diabetes and kidney problems.
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(Left) Detection of SARS-CoV-2 Spike S1 and Spike S1 RBD by Western Blot. Western blot depicting lysates from recombinant SARS-CoV-2 Spike S1 Subunit and recombinant SARS-CoV-2 Spike RBD probed with either (left blot) Mouse Anti-SARS-CoV-2 Spike S1 Monoclonal Antibody (Catalog # MAB105403) or (right blot) Mouse Anti-SARS-CoV-2 Spike S1 RBD Monoclonal Antibody (Catalog # MAB10540), followed by HRP-conjugated Anti-Mouse IgG Secondary Antibody (Catalog # HAF018). A specific band was detected for Spike S1 at approximately 90 kDa and for Spike S1 RBD at 35 kDa. (Right) Immunohistochemical detection of Spike S1 Subunit in human lung tissue infected with SARS delta variant. Spike S1 Subunit was detected in immersion fixed paraffin-embedded tissue sections of human lung infected with SARS-CoV-2 delta variant by probing with Mouse Anti-SARS-CoV-2 Spike S1 Monoclonal Antibody (Catalog # MAB105403) followed by detection with Anti-Mouse IgG VisUCyte™ HRP Polymer Antibody (Catalog # VC001). Prior to addition of the primary antibody, tissue was subjected to heat-induced epitope retrieval using VisUCyte Antigen Retrieval Reagent-Basic (Catalog # VCTS021). Tissue was stained using DAB (brown) and counterstained with hematoxylin (blue). Specific SARS-CoV-2 Spike S1 staining was localized to cytoplasm in bronchial epithelial cells. |
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A longitudinal cohort study by Ballering et al. involving 76,422 patients concluded that about one in eight patients suffer from symptom(s) that can only be attributed to a previous COVID infection. Since COVID affects multiple organs, several hypotheses exist to explain PCC: perturbance of microbiota-gut-brain axis, autoimmunity, tissue damage, or chronic inflammation. Whether long COVID represents a hidden infection or COVID-induced exacerbation of some pre-existent condition(s) is still up for debate.
However, some patients’ symptoms may be unrelated to COVID since the pre-COVID situation was not as rigorously recorded as the post-COVID scenario. Lack of accurate pre-COVID data limits researchers’ understanding of the disease. As scientists are unlocking the mysteries of COVID, PAIS has garnered renewed attention and the funding for COVID research is likely to rub off on other infections.
Spike RBD in HEK293 Human Cell Line Transfected with SARS-CoV-2 B.1.351S. Immunocytochemical analysis of Spike RBD detected in immersion fixed HEK293 human embryonic kidney cell line transfected with SARS-CoV-2 B.1.351S (positive staining) and wild type, non-transfected HEK293 cell line (negative staining) using Mouse Anti-SARS-CoV-2 B.1.351S Spike RBD Monoclonal Antibody (Catalog # MAB11024) and detected in cell via staining with NorthernLights™ 557-conjugated Anti-Mouse IgG Secondary Antibody (red; Catalog # NL007) and counterstaining with DAPI (blue). Specific Spike RBD staining was localized to cytoplasm.
The risk factors for PCC mainly include obesity, age between 35-65 years, female sex, underlying conditions such as asthma, and lower socioeconomic status. All-time COVID cases and deaths have exceeded 640 million and 6.6 million, respectively. Although SARS-CoV-2 infection is in decline, many people report at least one symptom that persists for two or more months after COVID diagnosis or recovery. At least half of the hospitalized patients do not fully recover from COVID. Thankfully, only a minority faces severe symptoms.
Example data from SARS-CoV-2 Variant Inhibitor Screening Kit using vaccinated donor samples using Wild Type or the Delta and Omicron Variants. Plasma samples from two donors (Donor 1: A-C; Donor 2: D-F) were collected and analyzed over a time course of Pre-Vaccination (Pre-Vac), or after receiving the 1st Dose or 2nd Dose of the Moderna Vaccine. An increasing amount of blocking antibodies were present at higher samples Dilution Factors following each vaccine dose. Additionally, the two donors had different blocking antibody levels follow the 1st Dose and 2nd Dose of the vaccine. The SARS-CoV-2 Variant Inhibitor Screening Kit (Catalog #VANC00B) was used to measure the differences in blocking efficiency between ACE-2 associated with the WT, Delta, or Omicron variant.
Vaccination before infection or infection with omicron as opposed to previous variants have been shown to reduce the likelihood of long COVID. However, anti-COVID vaccines reduce the risk of PCC by just 15%. The multidimensional symptoms of long COVID are manageable, but no therapy exists primarily because the random nature of who is affected.
Humans will most likely co-exist with the virus for the years to come, but scientists emphasize the continued exploration of biomarkers for diagnosis, prognosis, and treatment options. They also rely heavily on patients’ experiences and feedback to accurately track long COVID and to see what works and what does not.
People must come to terms with the fact that there is no cure available for long COVID. The touted “treatments” like acupuncture, vitamin and other infusions, Botox, certain blood-filtering procedures, or hyperbaric oxygen are all unproven and they will leave your wallets empty and hopes crushed. What is certain is the fact that the best approach against PCC is still the same old prevention strategy: wearing a mask, avoiding large gatherings, and getting vaccinated.
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Jamshed Arslan, Pharm D, PhD
Dr Arslan is an Assistant Professor at Salim Habib University (formerly, Barrett Hodgson University), Pakistan. His interest lies in neuropharmacology and preparing future pharmacists.
References
Antonelli M, Penfold RS, Merino J, et al. Risk factors and disease profile of post-vaccination SARS-CoV-2 infection in UK users of the COVID Symptom Study app: a prospective, community-based, nested, case-control study. Lancet Infect Dis. 2022;22(1):43-55. https://doi.org/10.1016/S1473-3099(21)00460-6
Antonelli M, Pujol JC, Spector TD, Ourselin S, Steves CJ. Risk of long COVID associated with delta versus omicron variants of SARS-CoV-2. Lancet. 2022;399(10343):2263-2264. https://doi.org/10.1016/S0140-6736(22)00941-2
Ballering AV, van Zon SKR, Olde Hartman TC, Rosmalen JGM; Lifelines Corona Research Initiative. Persistence of somatic symptoms after COVID-19 in the Netherlands: an observational cohort study. Lancet. 2022;400(10350):452-461. https://doi.org/10.1016/S0140-6736(22)01214-4
Centers for Disease Control and Prevention. “Long COVID or post-COVID conditions.” Sep. 1, 2022. https://www.cdc.gov/coronavirus/2019-ncov/long-term-effects/index.html
National Institutes of Health. “Long COVID.” Oct. 25, 2022. https://covid19.nih.gov/covid-19-topics/long-covid
Sellers FS. “Desperate covid long-haulers turn to costly, unproven treatments.” The Washington Post. Nov. 25, 2022. https://www.washingtonpost.com/health/2022/11/25/long-covid-treatments-unproven-brain-fog/
Thompson EJ, Williams DM, Walker AJ, et al. Long COVID burden and risk factors in 10 UK longitudinal studies and electronic health records. Nat Commun. 2022;13(1):3528. Published 2022 Jun 28. https://doi.org/10.1038/s41467-022-30836-0
Venkataramani V, Winkler F. Cognitive Deficits in Long Covid-19. N Engl J Med. 2022;387(19):1813-1815. https://doi.org/10.1056/NEJMcibr2210069
