Syndromic case definitions for Lower Respiratory Tract Infection (LRTI) are less sensitive in older age: an analysis of symptoms among hospitalised adults (preprint)

Background Lower Respiratory Tract Infections (LRTI) pose a serious threat to older adults but may be underdiagnosed due to atypical presentations. Here we assess LRTI symptom profiles and syndromic (symptom-based) case ascertainment in older (≥65y) as compared to younger adults (<65y). Methods We included adults (≥18y) with confirmed LRTI admitted to two acute care Trusts in Bristol, UK from 1st August 2020- 31st July 2022.  Logistic regression was used to assess whether age ≥65y reduced the probability of meeting syndromic LRTI case definitions, using patients’ symptoms at admission. We also calculated relative symptom frequencies (log-odds ratios) and evaluated how symptoms were clustered across different age groups. Results Of 17,620 clinically confirmed LRTI cases, 8,487 (48.1%) had symptoms meeting the case definition. Compared to those not meeting the definition these cases were younger, had less severe illness and were less likely to have received a SARS-CoV-2 vaccination or to have active SARS-CoV-2 infection. Prevalence of dementia/cognitive impairment and levels of comorbidity were lower in this group. After controlling for sex, dementia and comorbidities, age ≥65y significantly reduced the probability of meeting the case definition (aOR=0.67, 95% CI:0.63-0.71). Cases aged ≥65y were less likely to present with fever and LRTI-specific symptoms (e.g., pleurisy, sputum) than younger cases, and those aged ≥85y were characterised by lack of cough but frequent confusion and falls. Conclusions LRTI symptom profiles changed considerably with age in this hospitalised cohort. Standard screening protocols may fail to detect older and frailer cases of LRTI based on their symptoms.

Marked increase of interferon-ß after BNT162b2 mRNA vaccination: a case of polyarthritis with pleurisy.

Exacerbation of rheumatic disease after vaccination against SARS-CoV-2 is being reported. However, there are only a few cases of new-onset rheumatic diseases. We present two cases of new-onset persistent polyarthritis that developed in patients after receiving the mRNA vaccine against SARS-CoV-2. One patient had bilateral pleural effusions with markedly elevated serum interferon (IFN)-ß, while the other had no effusion, with serum IFN-ß comparable with that in healthy subjects. Other cytokines were unaltered in association with effusion. Both patients responded well to treatment with 20 mg prednisolone. Although more investigations are needed, the marked increase in serum IFN-ß levels observed in the case with pleural effusion may reflect an excessive response from the innate immune system to mRNA vaccines.

An Orally Available Cathepsin L Inhibitor Protects Lungs Against SARS-CoV-2-Induced Diffuse Alveolar Damage in African Green Monkeys (preprint)

The COVID-19 pandemic resulted from global infection by the SARS-CoV-2 coronavirus and rapidly emerged as an urgent health issue requiring effective treatments. To initiate infection, the Spike protein of SARS-CoV-2 requires proteolytic processing mediated by host proteases. Among the host proteases proposed to carry out this activation is the cysteine protease cathepsin L. Inhibiting cathepsin L has been proposed as a therapeutic strategy for treating COVID-19. SLV213 (K777) is an orally administered small molecule protease inhibitor that exhibits in vitro activity against a range of viruses, including SARS-CoV-2. To confirm efficacy in vivo, K777 was evaluated in an African green monkey (AGM) model of COVID-19. A pilot experiment was designed to test K777 in a prophylactic setting, animals were pre-treated with 100mg/kg K777 (N=4) or vehicle (N=2) before inoculation with SARS-CoV-2. Initial data demonstrated that K777 treatment reduced pulmonary pathology compared to vehicle-treated animals. A second study was designed to test activity in a therapeutic setting, with K777 treatment (33 mg/kg or 100 mg/kg) initiated 8 hours after exposure to the virus. In both experiments, animals received K777 daily via oral gavage for 7 days. Vehicle-treated animals exhibited higher lung weights, pleuritis, and diffuse alveolar damage. In contrast, lung pathology was reduced in K777-treated monkeys, and histopathological analyses confirmed the lack of diffuse alveolar damage. Antiviral effects were further demonstrated by quantitative reductions in viral load of samples collected from upper and lower airways. These preclinical data support the potential for early SLV213 treatment in COVID-19 patients to prevent severe lung pathology and disease progression.

Symptoms of Pleurisy as the Initial Presentation of COVID-19.

BACKGROUND Severe acute respiratory syndrome coronavirus 2, the virus responsible for Coronavirus Disease 2019 (COVID-19), has infected more than 8 million people worldwide and placed massive strains on healthcare systems around the world. Although classically causing cough, fever, and shortness of breath, increasing evidence suggests that manifestations of COVID-19 can be more subtle or masquerade as other clinical entities. CASE REPORT A 48-year-old man with hypertension and type 2 diabetes mellitus presented to the Emergency Department with acute-onset pleuritic chest pain that had developed 1 day earlier and was found to be hypoxemic, requiring supplemental oxygen. He was admitted under the internal medicine service and underwent an extensive workup for his chest pain and hypoxemia, including a negative computed tomography scan with pulmonary embolism protocol, negative nuclear medicine ventilation/perfusion scan, normal electrocardiogram, and normal echocardiography. In the end, he was diagnosed with viral pleuritis as the diagnosis of exclusion. Our patient subsequently developed a fever and shortness of breath and his nasopharyngeal swab performed on admission to hospital returned positive for COVID-19. The patient's pleuritic pain and oxygen requirements improved with supportive management over the next several days. CONCLUSIONS I report a patient who experienced pleuritic chest pain from viral pleurisy that was the initial manifestation of COVID-19 which, to the best of my knowledge, has not yet been reported in the literature. This case report further emphasizes that COVID-19 may present with atypical symptoms. It is crucial to be aware of these atypical presentations of COVID-19 so that patients are appropriately identified, isolated, and treated, while protecting health care workers from exposure.