July 2020 Update
Highlights from the International Conference on Covid-19
Kathleen Krafton, Brett Moskowitz, MA, Shambhavi Sohani, MPharm, and Axel Wirthmann, MD, PhD contributed to this update.
Medical experts from around the world gathered virtually on July 10-11 to share the latest research on SARS-CoV-2. This update provides a summary of the most clinically important highlights from the conference, including new information on antivirals, testing, management of hospitalized patients, protection of vulnerable populations, predictors of disease severity, vaccines, and the immune system response.
This was a professional conference where the information was largely intended for medical professionals. We have summarized our key findings for non-scientists interested in the latest research into the following bulleted list (the full report appears below):
Antivirals: hepatitis C drugs to the rescue? There are promising data on antivirals that increase the likelihood for a treatment breakthrough this fall. These include remdesivir, as well as 2 drugs already approved and successfully used to fight hepatitis C virus
Vaccines: they don’t have to be perfect to have an impact. An imperfect vaccine could still be a cost-effective and fundamental solution, especially if combined with continued social distancing measures and partial herd immunity
Testing: rapid and pooled testing will aid reopenings. Faster test results through rapid point-of-care testing and ramped up capacity through pooled testing of multiple samples at once may soon be on the way
Management: new tools for hospitalized patients. Anticoagulation therapy for hospitalized patients significantly reduces blood clots, which can occur even in those with mild or moderate disease
Understanding the gender gap: perception is reality. Women were significantly more likely than men to perceive COVID-19 as a risk and to view precautionary behaviors as effective. This may at least partially account for the significantly lower rate of hospitalizations and deaths among women compared to men.
Protecting the vulnerable: we know what works to prevent outbreaks. Urban areas, homeless shelters, and nursing facilities are more prone to outbreaks at least in part because population density is directly proportional to COVID-19 transmission rates
Predictors of disease severity: blood proteins provide new clues. Levels of certain proteins found in simple blood tests may be able to predict the severity of Covid-19 in newly diagnosed patients
The immune system response: it isn’t just about antibodies. Specific kinds of T-cells, which support the body’s immune response, show the potential to support recovery and immunity after SARS-CoV-2 infection. This could have implications for vaccine development. In addition, studies are underway to test the effects of T-cell-boosting with IL 7 treatment.
Full Report
Investigational Therapies
Perhaps the biggest treatment-related news to emerge from this conference is the reporting of promising data on a regimen including two antivirals already approved for the treatment of hepatitis C virus—the once-daily combination sofosbuvir (SOF) plus daclatasvir (DCV) 400/60mg. When added to standard therapy (which often included lopinavir/ritonavir (LPV/r) and/or hydroxychloroquine (HQN), the combination showed improved clinical recovery and a lower rate of death. A single study and a meta-analysis involving small Iranian trials of this treatment combination early in the pandemic were reported on by Anahita Sadeghi, Tehran University of Medical Science. In a multicenter, open-label, randomized study 29/33 patients (88%) achieved clinical recovery (resolution of fever, oxygen saturation levels, and respiratory rate) within 14 days compared to 22 patients (67%) on standard care alone (p=0.076). Patients were excluded from the trial if they had evidence of multi-organ failure prior to initiation of treatment, but only those with fever and evidence of chest involvement were included. The small number of patients (N-66) may account for the lack of a statistically significant difference between groups, though there is clearly a trend in favor of the SQV/DCV group. Statistical significance was reached when accounting for death as a competing risk: those in the SOF/DCV group recovered in a median 6 days (range of 4-10 days) versus 11 days (range of 6-17 days) for patients in the standard care alone group (p=0.041). In a meta-analysis in which this trial was combined with 2 other trials in Iran to evaluate a total of 176 patients, SOF/DCV showed a statistically significant benefit in the percentage of patients with clinical recovery within 14 days compared to standard of care (p=0.020). Among those taking SOF/DCV in the meta-analysis, 5/92 (5.4%) died compared to 17/84 (20%) patients given standard treatment (p=0.005), a 70% improvement. These results will be validated in the DISCOVER trial, which will recruit 600 patients in Iran and will compare SOF/DCV plus LPV/r to LPV/r alone with results expected in September 2020. Results from additional studies outside of Iran are expected in October.
Remdesivir (RDV) has been approved for compassionate use in hospitalized patients and is currently in wide use. A comparative analysis included 312 patients in a phase 3 RDV trial versus 818 patients on standard-of-care in a non-RDV retrospective cohort. The analysis showed that RDV was associated with significantly improved recovery by day 14, and a 62% reduction in odds of death in patients with severe COVID-19, according to Susan Olender, Columbia University Irving Medical Center. At day 14, 74.4% and 59.0% of patients in the RDV and non-RDV cohorts had recovered (adjusted odds ratio 2.03: 95% confidence interval 1.34-3.08, P<0.001). At day 14, 7.6% and 12.5% of patients in the RDV and non-RDV cohorts had died (adjusted odds ratio 0.38, 95% confidence interval: 0.22-0.68, P=0.001).
Outcomes in 86 pregnant and postpartum women treated with a 10-day course of compassionate use RDV for severe COVID-19 was associated with clinical improvement and no deaths. Richard Burwick, Cedars Sinai, reported data through May 20, 2020 on the 86 women who had clinical data for at least one day following treatment. There were 19 women with deliveries prior to their first dose re-classified as postpartum, 18 of whom were on mechanical ventilation or extracorporeal membrane oxygenation (ECMO), compared to 40% (27/67) of pregnant women. Oxygen support levels improved in 97% (65/67) and 90% (17/19) of pregnant and postpartum women, respectively, after median follow-up of 10 and 12 days. Among pregnant and postpartum women, 94% and 84% recovered to room air; 88% and 74% were discharged; 96% and 89% were extubated; and there were no maternal deaths.
Among 397 patients hospitalized at one of 55 sites in 8 countries in March 2020 with severe COVID-19 who were not yet on mechanical ventilation randomized to RDV for 5 or 10 days, more advanced pre-treatment respiratory disease severity, older age, Asian race, and certain comorbidities, predicted poorer clinical outcomes. according to Kristen Marks, Weill Cornell Medicine. The arms were ultimately combined for this analysis because of a lack of difference in efficacy between groups (the 5-day course is now recommended). Those requiring only low-flow oxygen or room air at baseline were significantly more likely to recover than those requiring ventilation or other high-grade oxygen support (HR=5.47; p<0.0001). And patients age <65 vs ≥65 years were significantly more likely to survive (HR=1.93). Black or White race (versus Asian race), ex-Italy regions, and no concomitant biologic medication were also associated with higher rates of clinical improvement. After a median 10 days of follow up, 44 patients (11%) had died and 256 (64%) showed ≥2-point improvement on a 7-category ordinal scale ranging from discharge to death (death-invasive mechanical ventilation-non-invasive ventilation-low-flow oxygen-room air with ongoing medical care-room air with no ongoing medical care-not hospitalized).
Convalescent plasma (CCP) is being studied across the world for its potential therapeutic efficacy in hospitalized patients with Covd-19 and preliminary reports are promising. However, neutralizing antibody titers (the titer indicates the number of times a solution can be diluted and still contain detectable amounts of a particular molecule) found in the first 68 patients (whose symptoms began 25–98 days prior) in a cohort reported on by Alena Markmann, University of North Carolina at Chapel Hill, vary widely between donors; therefore further studies are needed to determine what constitutes sufficient levels of anti-viral neutralizing antibody titers. If and when a certain level of neutralizing antibodies in CCP is determined to be a safe and efficacious treatment strategy, there will be a need for access to neutralization assays to ensure that sufficient anti-viral antibodies are contained in CCP banks. Male gender was associated with a higher ratio of neutralization titer. IgM positive donors had a higher median ratio of neutralization titer than IgM negative donors. Neither symptoms nor donor age was associated with neutralizing antibody titer among the first 20 donors. Further studies are needed to determine what neutralizing antibody titer is most clinically effective.
Vaccine Development
A partially-efficacious vaccine could also be a cost-effective fundamental solution for SARS-CoV-2 infection, according to Monia Makhoul from Weill Cornell Medicine-Qatar. An age-structured mathematical modeling analysis was conducted to determine the impact of vaccination on COVID-19 transmission and disease progression. A prophylactic vaccine with 69% efficacy could potentially prevent onset of the epidemic, while a vaccine with 50% efficacy could substantially reduce the susceptibility to infection.Through age-prioritization, vaccination in adults aged ≥20 years was effective in reducing the incidence of infection, while vaccination in adults aged ≥60 years was effective in reducing the number of deaths. Thus, as indicated by the study results, a vaccine with <70% efficacy could be impactful in controlling COVID-19 infection if it reduces infection duration in vaccinated individuals or is supplemented with a moderate reduction in contact rate or complemented with herd immunity.
Pooled Testing
An interesting new area of research that will possibly be fully operational in the US in the fall, according to an article in the New York Times, is pooled testing for Covid-19, which the FDA has already authorized for emergency use from one lab. The idea is to test samples taken from several individuals—at least 4 and potentially as many as 10 people at one time—in populations with a low prevalence of the virus so that most of your pooled results will be negative. At the same time, part of the sample from each person is preserved in case it needs to be retested. When there is a positive among the pooled test samples, the lab can go back and individually test the remaining samples to identify which person or persons is positive. With this method, you can test a much larger number of people in a timely fashion and it will improve the ability to track positivity rates and contact trace. A study from Thailand presented by Samadhi Patamatamkul, Mahasarakham University, showed that pool PCR testing up to 10 samples can detect a single SARS-CoV-2 positive sample within the pool. Three sets of deactivated SARS-CoV-2 samples derived from viral culture provided a pool size 5 and 10 and underwent real-time reverse transcriptase PCR (rRT-PCR). All pooled samples detected SARS-CoV-2 nucleic acids.
Predictors of Disease Severity
Two large retrospective Spanish studies evaluating a combined total of more than 6000 patients confirmed that advanced age, male gender, the presence of comorbidities and abnormal laboratory values were associated with increased odds of death. In one of the studies, which included 2226 adult patients admitted to a major teaching hospital between February 25 and April 19, 2020, 460 died and 1766 were discharged, reported José Arribas, Hospital Universitario La Paz, Spain. All of the factors listed above were statistically significant predictors of mortality in these patients. Risk increased is a stepwise manner with age group. In total, 1.5% of hospitalized patients ages 40-49 died, compared to 3.8% of those ages 50-59 and 11% of those ages 60-70. More than 30%, 50%, and 60% of patients ages 70-79, 80-89, and ≥90 years of age, respectively, died. The overall mortality rate for men was 26.6% versus 15.1% for women. Of the 460 patients who died, 448 (97.4%) had at least one comorbidity.
In the second study, which reported on over 4035 consecutive patients across 127 hospital centers across Spain until March 17, 2020 and followed them for at least 30 days, death occurred in 54.9% of those ≥80 years, 47.7% of those with 3 or more comorbidities at baseline, 45.7% of those requiring mechanical ventilation, and 42.4% of those admitted to the ICU, reported Juan Berenguer, Hospital General Universitario Gregorio Marañónmale. The overall mortality rate was 28%, with several factors independently associated with an increased hazard of death, including male sex, older age, arterial hypertension, obesity, liver cirrhosis, cancer, dementia, dyspnea, confusion, lower oxygen saturation (SaO2) on room air, higher neutrophil-to-lymphocyte ratio, lower platelet count, prolonged INR, lower estimated glomerular filtration rate (eGFR), and higher concentrations of C reactive protein (CRP).
A delay in hospitalization of patients with potentially severe cases of Covid-19 was associated with poorer outcomes and an increased risk of prolonged viral shedding (defined as >17 days from symptom onset) in a retrospective study of 480 patients admitted to an Italian reference hospital between March and May 2020, reported Annalisa Mondi, National Institute for Infectious Diseases. A total of 54/480 patients (11.3%) died in this cohort, and 41 of those who died continued to show viral shedding on their last real-time PCR test. Among 426 patients who were discharged after symptom improvement, 122 (25.4%) continued to show viral shedding on their last in-hospital PCR test. The median number of days from symptom onset to viral clearance (2 consecutive negative PCR tests) was 17 days and 66% of patients overall experienced viral clearance. The estimated probability of viral clearance within 30 days was 87.3% as measured by Kaplan-Meier curve. Factors independently associated with statistically significant higher rates of prolonged viral shedding included the number of days of symptoms prior to hospitalization, having at least one comorbidity at baseline, and lower levels of oxygen saturation at baseline. Slower viral clearance was associated with all of the above factors, as well as with immunomodulatory therapy during hospitalization. Although clinical recovery is strongly associated with viral clearance, the relationship between viral clearance and risk of invasive mechanical ventilation or death is not statistically significant.
Detectable blood plasma viremia is observed in high rates and is associated with increased mortality among patients hospitalized with SARS-CoV-2, according to a study presented by James Regan, Brigham and Women's Hospital. Plasma was collected from 74 hospitalized patients (median age 57 years, 19% on room air, 36% receiving supplemental oxygen by nasal cannula and 45% intubated) as well as outpatients with mild disease and individuals with resolved infection. A control group consisted of hospitalized individuals from the pre-Covid-19 era. In addition to plasma collection in patients hospitalized with Covid-19, samples were also collected with nasopharyngeal swabs, oropharyngeal swabs, sputum, and urine. Among the 74 participants hospitalized with COVID-19, 40% had detectable plasma viremia on initial sampling compared to none of the outpatients, individuals with resolved infection, or pre-COVID era hospitalized controls. Nasopharyngeal swab viral loads were significantly correlated with both oropharyngeal swab and sputum viral loads (P<0.01 for both), but not with plasma viral load. Those with detectable plasma viremia had a significantly higher mortality rate: 31% vs 3%, P<0.01. The role of plasma viral load in disease pathogenesis and to assess risk of severe disease in patients with COVID-19 requires further study.
Complications Associated with Covid-19
An observational study found that 19 of the 77 (24.67%) non-severe patients (no respiratory failure upon admission) admitted to a hospital in Vitoria, Spain (out of a total of 1260 adult Covid-19 patients admissions) who received an angio CT between March 1 and April 30, 2020 had a pulmonary embolism (PE) and that those not on prophylactic anticoagulation within that group were twice as likely to have a PE. The results were reported by Ana Martinez-Muñoz, Hospital Universitario de Alava. Among those with a PE, laboratory parameter dissociation—an excessively high D-Dimer with low CRP and normal lymphocytes—was the reason for the order of an angio CT to evaluate PE in nearly 80% of patients. In addition, anticoagulation treatment with low molecular weight heparin (LMWH) appears to decrease the incidence of PE. Hypertension and obesity were the most common comorbidities in patients with PE. It is unclear from the study poster how many of the 1260 patients admitted to the hospital during the retrospective study period had non-severe disease and therefore we cannot report what percentage of non-severe patients received an angio CT or PE diagnosis.
Gender Disparities in Perceived COVID-19 risk
Among 806 surveyed individuals, women were significantly more likely than men to perceive COVID-19 as a risk and to view precautionary behaviors as effective. Grace Yi, Johns Hopkins Bloomberg School of Public Health, reported data from an online crowd-sourcing survey. Among the 806 respondents, 44.5% were women and 55.5% were men. A significantly greater percentage of women reported frequent handwashing and social distancing. An independent association was found between handwashing and being female, having seniors in the household, and viewing precautionary measures as effective. Social distancing was independently associated with educational achievement, increased informational trust, and increased perception of COVID-19 as a threat (vulnerability to and severity of illness). The relationship between threat perception and social distancing was significantly modified by gender, with an effect 2.93 times greater for women than men.
Transmission Dynamics
The population density in US counties is directly proportional to the rates of COVID-19 transmission, as noted by Karla Therese L. Sy from Boston University School of Public Health. An increased contact rate in areas with a dense population was a potential factor for this relationship, which is partially modified by the primary mode of transportation. Around 36% of the counties in the US were included for analysis. The transmissibility of pathogens is described by a basic reproductive number R0, which significantly increased on average by 0.11 [95% CI=0.09 to 0.13] on doubling of the population density. Differential R0 by population density can assist in proper planning and resource allocation through more accurate predictions of the rate of COVID-19 spread in areas without active cases.
Transmission clusters in Spain and Italy continued to spread well before the lockdowns were ordered. The explosion of new cases in Spain was due to the emergence of at least four locally transmitted clusters that were already circulating not later than mid-February—a month before the lockdown—as suggested in a study presented by Francisco Diez-Fuertes from Hospital Clinic– IDIBAPS. There was also a simultaneous extension of transmission clusters with time until the containment effects of lockdown started showing up in Italy, according to Assunta Navarra from the National Institute for Infectious Diseases. Human mobility has been a major factor in transmission. However, mobility fluxes analysis detected clusters with higher relative risk in areas with different patterns of mobility. Hence, the study findings suggested that different dynamics of spread may contribute to the epidemic.
Epidemiology
Continued social distancing remains important regardless of widespread testing, case isolation and contact tracing for the prevention of rapid re-emergence of SARS CoV-2, according to a study presented by Dobromir Dimitrov from Fred Hutchinson Cancer Research Center. Mathematical modeling analysis conducted in King County in Washington State found that full implementation of physical distancing measures reduced transmission by ~65%. The model estimated ~35% pre-COVID physical interactions (pC_PI) under lockdown. With current levels of testing, maintaining less than 45% pC_PI is necessary. An increase in testing and isolation of symptomatic infections would allow some relaxation to current levels of physical distancing without a significant surge in local cases and deaths. However, these measures alone are insufficient to eliminate community transmissions. Thus, strict mask-wearing policies and the elimination of large gatherings become inevitable.
In Laos—where a total of 19 cases and 0 deaths have been reported—businesses and schools were closed prior to any confirmed cases of COVID-19. Two confirmed cases were reported in late March, which prompted increased testing and contact tracing, reported Kelley Khamphouxay, Save the Children International. Early intervention measures included prioritizing public trust and effective risk communication, expanding the national emergency hotline, and coordinating public messaging for accuracy and uniformity to counter the spread of inaccurate information on social media platforms. Pharmacies were provided with educational materials and referred individuals displaying symptoms to official testing centers. Information and training was widely shared among Laos’ Local Health System Sustainability project, which supported emergency operations teams that traveled to high-risk provinces to help coordinate local response efforts.
Thirty-five municipalities in Mexico, which make up only 14.2% of the country’s population, accounted for 48.8% of total COVID-19 deaths, as observed in a study presented by Enrique Bravo-García from Spectrum: Educación, Salud y Sociedad, AC. These municipalities have high population mobility and tourist spots. The study considered the background that an important sector of the Mexican population was not aware of the COVID-19 disease existence when 2.1% of the worldwide COVID-19 deaths were from the country. The results pointed out that mandatory social confinement, massive testing, and timely care for the infected could only help relieve the situation.
Latinx residents in the Mission district of San Francisco, California had an estimated 20-fold higher rate of PCR+ infections as compared with non-Latinx residents 6 weeks into a shelter-in-place order,according to a study presented by Gabriel Chamie from the University of California. Latinx people make up 39% of the population of California. With more than half of the COVID-19 cases in California found in this community, this study aimed to characterize community transmission during the shelter-in-place mandate. The second-most densely populated census tract in San Francisco was selected for the study. Mass, low-barrier SARS-CoV-2 reverse transcription-PCR and antibody testing were conducted in the community members, regardless of symptoms, over 4 days. A majority of the infections among the Latinx community members were asymptomatic, and recent infections were concentrated among people with low wages who were unable to work from home. These results contributed to the introduction of a social protection program in San Francisco to provide funding to the COVID-19 infected low-income group and to allow them to stay at home for self-quarantine.
Active surveillance and widespread testing among homeless shelter residents and staff, regardless of symptoms, may help to reduce COVID-19 transmission in this vulnerable population. Elizabeth Imbert, University of California San Francisco, reported data from a study of a COVID-19 outbreak in the largest homeless shelter in San Francisco (44,769 square feet). Immediately after 2 residents tested positive for COVID-19 in early April, the San Francisco Department of Public Health initiated case investigations, identifying close contacts and bedmates within 6 feet of the infected residents, who had since been moved to hotel rooms. Symptom screening of all residents was performed, and those with symptoms were tested. Seven additional residents tested positive and were relocated to hotel rooms. The department subsequently attempted to test all residents, which continued even after the shelter was closed on April 11 and all residents were relocated to hotel rooms. In total, 149 of 255 residents were tested, and 101 (68%) residents tested positive, 53 (52%) of whom were asymptomatic at the time of testing. Testing was also performed in 61 of 65 staff members who were present during the infectious period, 10 of whom (16%) tested positive. The high proportion of asymptomatic cases among both residents and shelter personnel suggests the futility of symptomatic testing in this high-risk population and the ease with which superspreading events could occur.
Markers of Disease Severity
The severity of Covid-19 in newly diagnosed patients may be predictable by looking at the expression of specific blood protein markers, reported Ayodele Alaiya, The King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia. Genetic expression of 99 of 144 identified plasma proteins were significantly associated with one of 4 Covid-19 patient clusters: asymptomatic, mild, moderate, or severe. These results open the way for the better identification of COVID-19 patients at higher risk for severe disease. More significant numbers of cases are required to develop standards that would also make it possible to predict the course of the disease.
Pathogenesis
Abundant ACE2 expression in the motile cilia of airway epithelial cells in the nasal cavity on down into the lower respiratory tract may account for the high transmissibility of the virus, according to Ivan Lee, Department of Pathology, Stanford University School of Medicine. The ACE2 expression in the nasal cavity cilia represents a vast "entry door" with an extensive surface area for SARS-CoV-2 virus binding. But ACE2 expression is not increased by ACE inhibitors like angiotensin-receptor-blockers (ARBs), alleviating concerns that the use of ACE inhibitors and ARBs is partly responsible for disease virulence and deterioration of the healthy renin-angiotensin-aldosterone system (RAAS) which is responsible for regulation of blood pressure. Indeed, these results provide the first mechanism-based evidence that the use of ACE inhibitors or ARBs does not increase susceptibility to SARS-CoV-2 infection via its ciliary ACE2 receptors in the upper respiratory tract. The authors underscore the need for an expeditious exploration of nasally administered therapeutics to block SARS-CoV-2 entry through the ciliary ACE2 receptor.
Covid-19 attacks four types of lung epithelial stem cells, including angiotensin-converting-enzyme 2 (ACE2), according to Anna Valyaeva, faculty of bioengineering and bioinformatics, Lomonosov Moscow State University. The research team analyzed publicly available RNA sequence data sets. The results demonstrated that four different lung epithelial stem cell types express SARS-CoV-2 entry factors, including ACE2, the entry receptor to which this new virus docks with the help of its spike proteins, eventually entering the cell. As a result, these stem cells, capable of replenishing lung epithelial cells, are significantly reduced in numbers, which leads to defects in regeneration capacity and accounts for the severity of infection. The severe damage of the gas-exchanging alveoli renders this tissue incapable of transferring the necessary amount of oxygen into the bloodstream, even by ventilators. The disturbance of the regeneration of the healthy cells of the lower respiratory tract has a greater impact on older adults who have a reduced general stockpile of stem cells.
Immunology
The immune system of 29 convalescent individuals all induced IgM, IgG, and IgA antibodies against the spike protein of SARS-CoV-2, according to Jeromine Klingler, Division of Infectious Diseases, Department of Medicine, Icahn School Of Medicine At Mount Sinai, New York. The team studied the antibody profiles of 29 convalescent SARS-CoV-2 infected individuals as well as longitudinal samples of two actively ill patients within three weeks of symptom onset. Their findings not only open the possibility to identify individuals of being convalescent after disease but also the development of a vaccine because neutralizing activity was detected in sera/plasma of all convalescent individuals.
SARS-CoV-2 specific T-cells exhibit the potential to support recovery and immunity after infection with Covid-19. IL 7 treatment is currently being tested in clinical trials to potentially expand SARS-CoV-2 specific T-cells, according to Nadia Roan, Department of Urology, University Of California, San Francisco. T-cells are likely essential for recovery from and immunity to SARS-CoV-2. However, SARS-CoV-2-specific T-cell phenotypes have not yet been clearly described. The investigation revealed that convalescent individuals show a diverse collection of spike-specific CD4+ T-cells that exhibit the potential to durably proliferate and enhance the expression of the IL7 receptor. These data support an essential role for SARS-CoV-2 specific T-cells in host control of COVID-19.
Mental Health
Adult depressive symptoms are associated with the perceived risk of COVID-19 infection and childhood trauma, according to Andrew Kim from the University of the Witwatersrand. Greater perceived risk of COVID-19 infection resulted in greater depressive symptoms and the link between perceived risk and depression was more severe among adults with ugly histories of childhood trauma. The study was conducted in uninfected adults from urban South Africa. The COVID-19 pandemic has affected individuals not just physically but also mentally. New social situations following the pandemic, inability to distancing due to adverse socioeconomic conditions, and loneliness are some of the factors contributing to the mental health of an individual, irrespective of the presence of COVID-19 infection. The study results emphasized the need for greater emergency mental health resources and sustainable improvements in public healthcare systems.